COMPREHENSIVE CALCULATION-BASED IMRT QA USING R&V DATA, TREATMENT RECORDS, AND A SECOND TREATMENT PLANNING SYSTEM

Purpose: Traditional patient-specific IMRT QA measurements are labor intensive and consume machine time. Calculation-based IMRT QA methods typically are not comprehensive. We have developed a comprehensive calculation-based IMRT QA method to detect uncertainties introduced by the initial dose calculation, the data transfer through the Record-and-Verify (R&V) system, and various aspects of the physical delivery. Methods: We recomputed the treatment plans in the patient geometry for 48 cases using data from the R&V, and from the delivery unit to calculate the “as-transferred” and “as-delivered” doses respectively. These data were sent to the original TPS to verify transfer and delivery or to a second TPS to verify the original calculation. For each dataset we examined the dose computed from the R&V record (RV) and from the delivery records (Tx), and the dose computed with a second verification TPS (vTPS). Each verification dose was compared to the clinical dose distribution using 3D gamma analysis and by comparison of mean dose and ROI-specific dose levels to target volumes. Plans were also compared to IMRT QA absolute and relative dose measurements. Results: The average 3D gamma passing percentages using 3%-3mm, 2%-2mm, and 1%-1mm criteria for the RV plan were 100.0 (σ=0.0), 100.0 (σ=0.0), and 100.0 (σ=0.1); for the Tx plan they were 100.0 (σ=0.0), 100.0 (σ=0.0), and 99.0 (σ=1.4); and for the vTPS plan they were 99.3 (σ=0.6), 97.2 (σ=1.5), and 79.0 (σ=8.6). When comparing target volume doses in the RV, Tx, and vTPS plans to the clinical plans, the average ratios of ROI mean doses were 0.999 (σ=0.001), 1.001 (σ=0.002), and 0.990 (σ=0.009) and ROI-specific dose levels were 0.999 (σ=0.001), 1.001 (σ=0.002), and 0.980 (σ=0.043), respectively. Comparing the clinical, RV, TR, and vTPS calculated doses to the IMRT QA measurements for all 48 patients, the average ratios for absolute doses were 0.999 (σ=0.013), 0.998 (σ=0.013), 0.999 σ=0.015), and 0.990 (σ=0.012), respectively, and the average 2D gamma(5%-3mm) passing percentages for relative doses for 9 patients was were 99.36 (σ=0.68), 99.50 (σ=0.49), 99.13 (σ=0.84), and 98.76 (σ=1.66), respectively. Conclusions: Together with mechanical and dosimetric QA, our calculation-based IMRT QA method promises to minimize the need for patient-specific QA measurements by identifying outliers in need of further review.

BLyS/BAFF-R signaling pathway in human aggressive non Hodgkin's lymphoma B cell and normal peripheral blood B lymphocytes

B-lymphocyte stimulator (BLyS also called BAFF), is a potent cell survival factor expressed in many hematopoietic cells. BLyS levels are elevated in the serum of non-Hodgkin lymphoma (NHL) patients, and have been reported to be associated with disease progression, and prognosis. To understand the mechanisms involved in BLyS gene expression and regulation, we examined expression, function, and regulation of the BLyS gene in B cell non-Hodgkin's lymphoma (NHL-B) cells. BLyS is constitutively expressed in aggressive NHL-B cells including large B cell lymphoma (LBCL) and mantle cell lymphoma (MCL) contributing to survival and proliferation of malignant B cells. Two important transcription factors, NF-κB and NFAT, were found to be involved in regulating BLyS expression through at least one NF-κB and two NFAT binding sites in the BLyS promoter. Further study indicates that the constitutive activation of NF-κB and BLyS in NHL-B cells forms a positive feedback loop contributing to cell survival and proliferation. In order to further investigate BLyS signaling pathway, we studied the function of BAFF-R, a major BLyS receptor, on B cells survival and proliferation. Initial study revealed that BAFF-R was also found in the nucleus, in addition to its presence on plasma membrane of B cells. Nuclear presentation of BAFF-R can be increased by anti-IgM and soluble BLyS treatment in normal peripheral B lymphocytes. Inhibition of BLyS expression decreases nuclear BAFF-R level in LBCL cells. Furthermore, we showed that BAFF-R translocated to nucleus through the classic karyopherin pathway. A candidate nuclear localization sequence (NLS) was identified in the BAFF-R protein sequence and mutation of this putative NLS can block BAFF-R entering nucleus and LBCL cell proliferation. Further study showed that BAFF-R co-localized with NF-κB family member, c-rel in the nucleus. We also found BAFF-R mediated transcriptional activity, which could be increased by c-rel. We also found that nuclear BAFF-R could bind to the NF-κB binding site on the promoters of NF-κB target genes such as BLyS, CD154, Bcl-xL, Bfl-1/A1 and IL-8. These findings indicate that BAFF-R may also promote survival and proliferation of normal B cells and NHL-B cells by directly functioning as a transcriptional co-factor with NF-κB family member. ^