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D Yan

Publications and source records attributed to D Yan.

At least 73 records · Page 4Linked to original sources
PubMed1998

Experimental murine IgA nephropathy following passive administration of vomitoxin-induced IgA monoclonal antibodies.

Oral exposure of mice to vomitoxin (VT) induces elevated levels of serum IgA, circulating IgA immune complexes (IgA-IC), mesangial IgA deposition and haematuria, which all mimic the clinical signs of human IgA nephropathy (IgAN). To further assess the effects of VT-induced IgA in the murine model, B6C3F1 and BALB/C mice were injected intraperitoneally with affinity-purified monoclonal IgA derived from Peyer's patch hybridomas of VT-exposed mice. In B6C3F1 mice, serum IgA, IgM and IgA-IC levels were increased two- to fivefold in treatment groups after 4 and 6 wk compared with controls, whereas increases in serum IgG as high as 18-fold were observed. Urinary erythrocyte counts were also significantly elevated in treatment groups after 2, 4 and 6 wk compared with controls. Concurrent increases in IgA and IgG complexes containing casein, the dietary protein source, occurred in treatment mice. Mesangial IgA, IgG, IgM and C3 deposition were significantly increased in all treatment mice after 6 wk. Electron-dense deposits occurred in the glomeruli of IgA-injected mice after 6 wk. All the above parameters were similarly affected in BALB/C mice. Injection of IgA-secreting hybridoma cells into BALB/C mice increased serum IgA, IgA-IC and IgG levels as well as elevated mesangial IgA, IgG and C3 deposition and haematuria after 2-3 weeks compared with controls. In total, these data indicate that passive administration of VT-induced IgAs can induce the hallmarks of IgA nephropathy. Casein, an antigen found in the diet used for these mice, appeared to form IC with IgA or IgG and these IC may participate in the pathogenesis of this nephropathy.

Animals↗
PubMed1998

CUS2, a yeast homolog of human Tat-SF1, rescues function of misfolded U2 through an unusual RNA recognition motif.

A screen for suppressors of a U2 snRNA mutation identified CUS2, an atypical member of the RNA recognition motif (RRM) family of RNA binding proteins. CUS2 protein is associated with U2 RNA in splicing extracts and interacts with PRP11, a subunit of the conserved splicing factor SF3a. Absence of CUS2 renders certain U2 RNA folding mutants lethal, arguing that a normal activity of CUS2 is to help refold U2 into a structure favorable for its binding to SF3b and SF3a prior to spliceosome assembly. Both CUS2 function in vivo and the in vitro RNA binding activity of CUS2 are disrupted by mutation of the first RRM, suggesting that rescue of misfolded U2 involves the direct binding of CUS2. Human Tat-SF1, reported to stimulate Tat-specific, transactivating region-dependent human immunodeficiency virus transcription in vitro, is structurally similar to CUS2. Anti-Tat-SF1 antibodies coimmunoprecipitate SF3a66 (SAP62), the human homolog of PRP11, suggesting that Tat-SF1 has a parallel function in splicing in human cells.

Amino Acid Sequence↗
PubMed1997

Potential role for IL-5 and IL-6 in enhanced IgA secretion by Peyer's patch cells isolated from mice acutely exposed to vomitoxin.

Dietary exposure to vomitoxin (VT) results in hyperelevated serum IgA and IgA nephropathy in mice. To assess the possible role of cytokines in this IgA dysregulation, the effects of a single oral exposure in B6C3F1 male mice to 0, 5 or 25 mg/kg BW VT on production of IgA and cytokines in Peyer's patch (PP) and spleen cell cultures were evaluated. IgA levels were increased significantly in PP cell cultures prepared from mice at 2 or 24 h after oral exposure to VT and subsequently stimulated with phorbol myristate acetate (PMA) and ionomycin (ION) or with lipopolysaccharide (LPS). Significant effects on IgA production were not observed in spleen cell cultures. Since cytokines such as IL-2, IL-4, IL-5 and IL-6 have been shown to promote IgA production, the effect of the same VT exposure regimen on secretion of these mediators was determined in PP and spleen cultures. Supernatant IL-2 and IL-4 levels were unaffected by the prior treatment of animals with VT. In contrast, IL-5 levels were increased significantly in 7-day PP cell cultures obtained 2 h after VT exposure both with and without PMA + ION exposure but not in other cultures. IL-6 levels were increased significantly in LPS-treated cultures prepared from PP at 2 and 24 h following exposure to VT. IL-6 levels were also elevated significantly in both PMA + ION or LPS treated cultures from spleen isolated at 2 h but not 24 h post VT exposure. To determine whether IL-5 or IL-6 play a role in IgA hyperelevation in vitro, PP and spleen cells from mice obtained 2 h after exposure to 25 mg/kg VT were cultured in the presence of neutralizing cytokine antibodies (Abs) and IgA production was monitored. Consistent with IL-5's previously documented role in IgA production, anti-IL-5 decreased IgA levels to background in cultures of both control and VT-exposed PP or spleen cells in the presence of either PMA + ION or LPS. Similar results were seen with addition of anti-IL-6. IgA levels were decreased to a lesser extent in PP cells cultured with LPS and in spleen cells cultured with PMA + ION from VT-exposed mice to which anti-IL-2 Ab was added. Thus, the potential for enhanced IgA production exists in lymphocytes as early as 2 h and as late as 24 h after a single oral exposure to VT and this may be related to the increased capacity to secrete helper cytokines of T cell and macrophage origin. Taken together, the results suggest that the superinduction of cytokine expression may, in part, be responsible for upregulation of IgA secretion in mice exposed orally to VT.

Administration, Oral↗
PubMed1997

Adaptive modification of treatment planning to minimize the deleterious effects of treatment setup errors.

PURPOSE: Using daily setup variation measured from an electronic portal imaging device (EPID), radiation treatment of the individual patient can be adaptively reoptimized during the course of therapy. In this study, daily portal images were retrospectively examined to: (a) determine the number of initial days of portal imaging required to give adequate prediction of the systematic and random setup errors; and (b) explore the potential of using the prediction as feedback to reoptimize the individual treatment part-way through the treatment course. METHODS AND MATERIALS: Daily portal images of 64 cancer patients, whose treatment position was not adjusted during the course of treatment, were obtained from two independent clinics with similar setup procedures. Systematic and random setup errors for each patient were predicted using different numbers of initial portal measurements. The statistical confidence of the predictions was tested to determine the number of daily portal measurements needed to give reasonable predictions. Two treatment processes were simulated to examine the potential opportunity for setup margin reduction and dose escalation. The first process mimicked a conventional treatment. A constant margin was assigned to each treatment field to compensate for the average setup error of the patient population. A treatment dose was then prescribed with reference to a fixed normal tissue tolerance, and then fixed in the entire course of treatment. In the second process, the same treatment fields and prescribed dose were used only for the initial plan and treatment. After several initial days of treatments, the treatment field shape and position were assumed to be adaptively modified using a computer-controlled multileaf collimator (MLC) in light of the predicted systematic and random setup errors. The prescribed dose was then escalated until the same normal tissue tolerance, as determined in the first treatment process, was reached. RESULTS: The systematic setup error and the random setup error were predicted to be within +/-1 mm for the former and +/-0.5 mm for the latter at a > or = 95% confidence level using < or = 9 initial daily portal measurements. In the study, a large number of patients could be treated using a smaller field margin if the adaptive modification process were used. Simulation of the adaptive modification process for prostate treatment demonstrates that additional treatment dose could be safely applied to 64% of patients. CONCLUSION: The adaptive modification process represents a different approach for use of on-line portal images. The portal imaging information from the initial treatments is used as feedback for reoptimization of the treatment plan, rather than adjustment of the treatment setup. Results from the retrospective study show that the treatment of individual patient can be improved with the adaptive modification process.

Algorithms↗
PubMed1997

Differential cytokine mRNA expression in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): dose response and time course.

Acute oral exposure of B6C3F1 mice to vomitoxin (VT) has been previously shown to induce expression of mRNAs for cytokines that are characteristically produced in lymphoid tissues by macrophage and T cells. The purpose of this study was to evaluate the effects of VT dose on the expression of mRNAs for a cytokine profile consisting of TNF-alpha, IL-1beta, IL-6, IL-12, IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-12, and TGF-beta and to measure the kinetics of these responses. The effects of a single oral exposure to 0, 0.1, 0.5, 1, 5, and 25 mg/kg BW of VT on cytokine mRNA abundance in spleen and Peyer's patches (indicators of systemic and mucosal immune compartments, respectively) were assessed at 2 hr postexposure using reverse transcriptase-polymerase chain reaction (RT-PCR) in combination with hybridization analysis. Both 5 and 25 mg/kg VT significantly induced the mRNAs for the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha; the T helper 1 cytokines IFN-gamma and IL-2; and the T helper 2 cytokines IL-4 and IL-10, whereas lower doses had no effect. IL-12p40 mRNA was also induced but not IL-12p35 mRNA. The effects were more pronounced in spleen than in the Peyer's patches. IL-5 and TGF-beta mRNAs were expressed constitutively in spleen and Peyer's patches but were not affected by VT. When cytokine mRNA levels were measured at 1, 2, 4, 8, and 24 hr after oral exposure to 25 mg/kg BW of VT, mRNA expression kinetics varied among cytokines or between spleen and Peyer's patches. The duration of elevated mRNA expression in spleen was 1-8 hr for TNF-alpha, IL-6, IFN-gamma, and IL-10 and was 1-4 hr for IL-1beta, IL-12p40, IL-2, and IL-4. In Peyer's patches, duration periods were 1-8 hr for IL-6, IL-2, and IL-10; 1-4 hr for IL-1beta, IL-12p40, and TNF-alpha; and 1-2 hr for IFN-gamma. Serum levels of TNF-alpha, IL-6, and IFN-gamma were elevated 3 hr after exposure to 25 mg/kg VT, thus suggesting that elevation of splenic and Peyer's patch mRNA abundance correlated with increases in systemic production of these cytokines. Taken together, the results indicate that a single VT exposure rapidly induces gene expression in vivo for a wide range of cytokines with apparently complete recovery occurring after 24 hr. Elevated cytokine expression may play an important role in the pathophysiologic effects of VT and other trichothecenes.

Administration, Oral↗
PubMed1997

Adaptive radiation therapy.

Adaptive radiation therapy is a closed-loop radiation treatment process where the treatment plan can be modified using a systematic feedback of measurements. Adaptive radiation therapy intends to improve radiation treatment by systematically monitoring treatment variations and incorporating them to re-optimize the treatment plan early on during the course of treatment. In this process, field margin and treatment dose can be routinely customized to each individual patient to achieve a safe dose escalation.

Confidence Intervals↗
PubMed1997

[Changes and evaluation of indexes on treating ganyanghuafengzheng with cerebral infarction by tianlongxifeng granulae].

We used TIANLONGXIFENG granulae to treat the patients with GANYANGHUAFENGZHENG of cerebral infarction, and mobilely observed the contents of plasma norepinephrine, epinephrine, cortisol, thromboxane B2 and serum triiodothyroidoglobulin. The results showed that with the improvement of curative effect and the decrease of symptom scores, the contents of parameters mentioned above changed accordingly. It is suggested that these parameters may have value for diagnosis.

Adult↗
PubMed1997

A study on plasma norepinephrine and epinephrine levels in TCM liver syndromes.

The levels of plasma norepinephrine (NE) and epinephrine (E) were determined by HPLC in 220 patients with various TCM liver syndromes, and in 96 healthy subjects as controls. The plasma NE and E contents were higher in patients with liver excess syndromes, including Ganqi Yujie (GQYJ [symbol: see text]) syndrome, Ganyang Shangkang (GYSK [symbol: see text]) syndrome, Ganhuo Shangyan (GHSY [symbol: see text]) syndrome, and Ganyang Huafeng (GYHF [symbol: see text]) syndrome; while they were lower in patients with liver deficiency syndromes, including Ganqixu (GQX [symbol: see text]) syndrome, Ganxuexu (GXX [symbol: see text]) syndrome, and Ganyinxu (GYX [symbol: see text]) syndrome. Futhermore, when Ganshen Yinxu (GSYX [symbol: see text]) syndrome was turned into GYSK and then into GYHF, the plasma NE and E contents increased in order of precedence; while when GQYJ was turned into Ganyu Pixu (GYPX [symbol: see text]) syndrome, both NE and E contents decreased. The results suggest that the plasma NE and E contents are reliable objective parameters for the study of pathophysiological basis of the liver excess and liver deficiency syndromes, and the liver-kidney and liver-spleen interrelated syndromes.

Adolescent↗
PubMed1997

[Reconstruction of tendon sheath by autogenous vein graft in preventing adhesion].

In order to prevent tendon adhesion following operation, autogenous great saphenous vein graft was used to reconstruct the tendon sheath. The operation was performed under microsurgical technique. This method was used to repair 23 tendons and 17 tendon sheaths. The early functional exercises were carried out after operation. Follow up from 10 months to 4 years, the prognosis was good except in 3 fingers, in which, the wounds were infected resulting the necrosis of the grafted veins and exposure of the repaired tendons. The details of the operation were introduced. It was emphasized that non-traumatic handling of the tissues was essential in preventing tendon from adhesion.

Adult↗
PubMed1997

[The contents of plasma norepinephrine and epinephrine in patients with five types of Gan syndromes in TCM and its significance for diagnosis].

Plasma norepinephrine (NE) epinephrine (E) concentrations in patients with five types of Gan syndromes and relative syndromes were determined. The healthy individuals served as control. The contents of NE and E in Ganyang Huafeng Zheng (5975.8 +/- 305.6 pmol.L-1, 2227.7 +/- 12.57 pmol.L-1) were significantly increased; Ganxue Xu Zheng (1100.4 +/- 105.5, 451.2 +/- 70.9 pmol.L-1) were decreased, and lower than the normal controls. NE and E contents in both Ganyang Shangkang Zheng (3962.6 +/- 354.4, 1225.6 +/- 163.5 pmol.L-1) and Ganhuo Shangyan Zheng (3398.1 +/- 303.8, 1134.4 +/- 146.9 pmol.L-1) were increased remarkably, but there was no difference between them. Plasma NE, E concentrations can be considered as one of the comprehensive laboratory parameters in diagnosis of the four above mentioned Gan syndromes.

Adolescent↗
PubMed1996

Glutamate is required to maintain the steady-state potassium pool in Salmonella typhimurium.

In many bacteria, accumulation of K+ at high external osmolalities is accompanied by accumulation of glutamate. To determine whether there is an obligatory relationship between glutamate and K+ pools, we studied mutant strains of Salmonella typhimurium with defects in glutamate synthesis. Enteric bacteria synthesize glutamate by the combined action of glutamine synthetase and glutamate synthase (GS/GOGAT cycle) or the action of biosynthetic glutamate dehydrogenase (GDH). Activity of the GS/GOGAT cycle is required under nitrogen-limiting conditions and is decreased at high external ammonium/ammonia ((NH4)+) concentrations by lowered synthesis of GS and a decrease in its catalytic activity due to covalent modification (adenylylation by GS adenylyltransferase). By contrast, GDH functions efficiently only at high external (NH4)+ concentrations, because it has a low affinity for (NH4)+. When grown at low concentrations of (NH4)+ (< or = 2 mM), mutant strains of S. typhimurium that lack GOGAT and therefore are dependent on GDH have a low glutamate pool and grow slowly; we now demonstrate that they have a low K+ pool. When subjected to a sudden (NH4)+ upshift, strains lacking GS adenylyltransferase drain their glutamate pool into glutamine and grow very slowly; we now find that they also drain their K+ pool. Restoration of the glutamate pool in these strains at late times after shift was accompanied by restoration of the K+ pool and a normal growth rate. Taken together, the results indicate that glutamate is required to maintain the steady-state K+ pool -- apparently no other anion can substitute as a counter-ion for free K+ -- and that K+ glutamate is required for optimal growth.

Glutamic Acid↗
PubMed1996

Invariant U2 RNA sequences bordering the branchpoint recognition region are essential for interaction with yeast SF3a and SF3b subunits.

U2 small nuclear RNA (snRNA) contains a sequence (GUAGUA) that pairs with the intron branchpoint during splicing. This sequence is contained within a longer invariant sequence of unknown secondary structure and function that extends between U2 and I and stem IIa. A part of this region has been proposed to pair with U6 in a structure called helix III. We made mutations to test the function of these nucleotides in yeast U2 snRNA. Most single base changes cause no obvious growth defects; however, several single and double mutations are lethal or conditional lethal and cause a block before the first step of splicing. We used U6 compensatory mutations to assess the contribution of helix III and found that if it forms, helix III is dispensable for splicing in Saccharomyces cerevisiae. On the other hand, mutations in known protein components of the splicing apparatus suppress or enhance the phenotypes of mutations within the invariant sequence that connect the branchpoint recognition sequence to stem IIa. Lethal mutations in the region are suppressed by Cus1-54p, a mutant yeast splicing factor homologous to a mammalian SF3b subunit. Synthetic lethal interactions show that this region collaborates with the DEAD-box protein Prp5p and the yeast SF3a subunits Prp9p, Prp11p, and Prp21p. Together, the data show that the highly conserved RNA element downstream of the branchpoint recognition sequence of U2 snRNA in yeast cells functions primarily with the proteins that make up SF3 rather than with U6 snRNA.

Base Sequence↗
PubMed1995

Dosimetric evaluation of the conformation of the multileaf collimator to irregularly shaped fields.

PURPOSE: The goal of this study was to evaluate the dosimetric characteristics of geometric MLC prescription strategies and compare them to those of conventional shielding block. METHODS AND MATERIALS: Circular fields, square fields, and 12 irregular fields for patients with cancer of the head and neck, lung, and pelvis were included in this study. All fields were shaped using the MLC and conventional blocks. A geometric criterion was defined as the amount of area discrepancy between the MLC and the prescription outline. The "least area discrepancy" (LAD) of the MLC conformation was searched by selecting the collimator angle, meanwhile keeping a preselected position along the width of the leaf into the prescribed field. Five LAD conventions were studied. These included the LAD-0, LAD-1/3, LAD-1/2, and LAD-2/3 that inserted the leaves at the 0, 1/3, 1/2, and 2/3 of the leaf end into the prescription field, respectively. In addition, the LAD optimization was applied to the transecting (TRN) approach for leaf conformation that prescribed an equal area of overblocking and underblocking under each leaf. Film dosimetry was performed in a 20 cm polystyrene phantom at 10 cm depth 100 cm from source to axis distance (SAD) for both 6 and 18 MV photons with each of the above MLC conformations and conventional blocks. The field penumbra width, defined as the mean of the separation between the 20% and 80% isodose lines along the normal of the prescription field edge, was calculated using both the MLC and conventional block film dosimetry and compared. In a similar way, the d20 is defined as the mean separation between the 20% isodose line and the prescription field edge, and the d80 is defined as the mean separation between the 80% isodose line and the prescription field edge. RESULTS: The field penumbra width for all MLC conventions was approximately 2 mm larger than that of the conventional block. However, there was a larger variation of the separation distribution in the penumbra region of the irregular fields for the MLC, which had a standard deviation of 1 mm (a factor of 5 larger than the conventional block). The dosimetry for the circular fields showed that the LAD-TRN, LAD-1/2, and LAD-1/3 approximated the conventional blocking well in terms of d20 and d80; however, no single convention produced the best conformation for both measures. The dosimetric result of the patient treatment fields was similar for all sites. The LAD-1/3, LAD-1/2, and LAD-TRN strategies conformed to within 1 to 1.5 mm of the d80 of the conventional block for both 6 MV and 18 MV, respectively. The LAD-1/2 and LAD-TRN conformations were virtually identical, although it is proven analytically that the LAD-1/2 convention has the least overall area discrepancy of all conventions. CONCLUSIONS: The five MLC conformation conventions resulted in similar dosimetric penumbrae for all field shapes studied. The LAD-1/3, LAD-TRN, and LAD-1/2 produced the more favorable approximation to conventional block. The field penumbra width, although useful for evaluating irregular field shapes, could not describe the large local variations in the penumbra along the field edge for the MLC. These local variations could be of clinical concern when they appear near vital organs. However, the variation in a local region can potentially be reduced by minimizing the jaggedness of the leaf steps in that local region. The dosimetric results were useful as guidelines for the clinicians in the evaluation and adjustment of MLC leaf positions.

Head and Neck Neoplasms↗
PubMed1995

Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial.

PURPOSE: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. METHODS AND MATERIALS: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. RESULTS: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. CONCLUSIONS: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system.

Adenocarcinoma↗
PubMed1995

The cumulative verification image analysis tool for offline evaluation of portal images.

PURPOSE: Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. METHODS AND MATERIALS: The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tool's operation is repeated in the analysis of daily portal images. RESULTS: The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for treatment plan recalculation and to test various decision strategies for treatment adjustment. CONCLUSIONS: The CVIA tool provides comprehensive analysis of daily images acquired with electronic portal imaging devices. Its offline approach allows characterization of the nature of setup variation for the individual patient that would have been difficult to deduce using only a few daily or weekly portal images. Distribution of the tool will help establish an important database of setup variation from many clinics. The information derived from CVIA can also serve as the foundation to integrate treatment verification, treatment planning, and treatment delivery.

Computer Peripherals↗
PubMed1995

Effects of treatment setup variation on beam's eye view dosimetry for radiation therapy using the multileaf collimator vs. the cerrobend block.

PURPOSE: The purpose of this study is to quantify and compare retrospectively the effects of treatment setup variation on beam's eye view (BEV) dosimetry for radiation therapy using a multileaf collimator (MLC) vs. cerrobend block. METHODS AND MATERIALS: A study was performed on a group of 18 patients with cancer of the head and neck, lung, and pelvis who were treated with irregularly shaped fields. The BEV dosimetry of the fields shaped with cerrobend blocks and the MLC was measured with films at the depth of dose prescription in a solid water phantom. A "one-half-leaf" insertion convention was used to shape the MLC. In addition, an average of 15 sequential daily port films was taken per patient during the course of radiotherapy. The port films were aligned with the prescription film for each patient. Systematic error and random error of treatment setup for each patient were calculated. The effects of setup variation were incorporated by convolving the patient portal imaging data with the corresponding BEV film dosimetry. Two parameters were used to quantify the BEV dosimetry. First, the field penumbra width was calculated, which represented the average of the normal separations between 20 and 80% isodose lines along the prescription outline. Second, the ratio of areas covered by the 90 and 20% isodose lines, A90/20, was determined. The BEV dosimetry was then characterized with and without the effects of treatment setup variation. In addition, the difference in BEV dosimetry between the cerrobend block and the MLC was used to estimate the corresponding changes in tumor control probability (TCP). These changes were also compared to the changes in TCP for the treatment with or without the effects of random setup variation. RESULTS: With or without daily setup variation, the use of cerrobend block was more favorable than the MLC in terms of the field penumbra width and A90/20 for all treatment sites. In the absence of daily variation, the MLC field penumbra width was on average 1.3 mm larger than that of the cerrobend block, and 0.9 mm larger in the presence of daily setup variation. Similarly, the ratio A90/20 of the cerrobend block was on average 0.03 larger than that of MLC without daily setup variation, and 0.02 with daily setup variation. The difference in field penumbra width and A90/20 between the MLC and the cerrobend block was slightly reduced due to the effects of daily setup variation. For both the cerrobend block and the MLC, daily setup variation produced a significant increase in the field penumbra width, 2.3 mm for the cerrobend block and 1.9 mm for the MLC, and a decrease in the A90/20, 0.06 for the former and 0.05 for the latter. The change due to the daily setup variation was about a factor of 2 larger than the changes due to replacing the cerrobend block with the MLC. Using the TCP model, the change in TCP due to the daily setup variation was more than a factor of 3 larger than the change in TCP due to replacing the cerrobend block with the MLC. It was noted that the average changes in the penumbra, the A90/20 and the TCP calculated for the patient population did not adequately describe the changes for the individual patient. CONCLUSION: Our results do not show significant dosimetric differences between the MLC and the cerrobend block in conventional radiation treatment, whether or not daily setup variation was taken into consideration. The effects of daily setup variation alone produced a larger dosimetric change. The same results were obtained when the data were applied to calculate changes in TCP. For optimal radiation therapy, efforts should be concentrated on reducing daily setup variation. Our results also demonstrate the importance of frequent evaluation of MLC treatment using electronic portal imaging devices.

Equipment Design↗
PubMed1995

Intraoperative optimization of needle placement and dwell times for conformal prostate brachytherapy.

PURPOSE: Traditionally, transperineal prostate brachytherapy has been heavily operator dependent. To overcome this limitation, a treatment planning method was developed for intraoperative planning, guidance, and evaluation. In this setting, reliability, speed, and ease of understanding are primary considerations. This planning method has been implemented for ultrasound guided implants of the prostate, but can be extended for use in other body sites. METHODS AND MATERIALS: The length and cross-section of the target (prostate) and location of urethra and rectum are determined intraoperatively from live ultrasound imaging. The planning program then automatically generates a "reference plan" containing needle locations, dwell times, and the resulting isodose distribution. As needles are placed, this information is corrected to account for any deviation of needle placement or movement of the prostate. Once all needles are in place, the normalization is adjusted to reconcile remaining hot-spots with coverage of the target volume. Optimization is performed in three separate stages. Each stage works to enhance only a subset of the implant parameters. (a) Pattern Optimization attempts to find the most appropriate placement for the needles or catheters. It is based on the transverse contour of the target volume. Needles are placed uniformly around the perimeter, and interior needle positions are determined from the cross-sectional area and shape. Critical structures such as the urethra are explicitly avoided. This step provides the overall framework for the implant, and is not generally repeated. (b) Relative Dwell Time Optimization selects relative dwell times that will give the best uniformity of dose. It works by setting the relative dwell time in each source position inversely proportional to the dose delivered to that point by the other source positions. It is used in the reference plan, and is repeated as each needle is inserted. This provides dosimetric feedback to the physician, who can judge the effect of deviations from the reference plan. (c) Relative Volume Optimization is an interactive method for fine tuning the normalization based upon volume analysis. The volume analysis is presented in tabular and graphical form, both being updated rapidly as the normalization is adjusted. The information is formatted to help the operator judge coverage and uniformity. Special functions are provided that allow the operator to "jump" to special normalization values based on several indices of uniformity or uniformity/coverage. RESULTS: This system overcomes some conventional brachytherapy limitations. Rather than depend on the operator's intuitive judgement of where the needles should be placed, a global plan is generated and validated with full dose calculations. Immediate feedback is provided concerning the adequacy of placement and avoidance of critical structures. This information is provided in terms of actual tissue doses to the target volume and critical structures using point doses, isodose distributions, and volume analysis. Since the new method was introduced in January 1994, 33 implants have been performed. The needle placement method has been reliable in the clinic, with different doctors producing similar results on subsequent fractions for the same patient. CONCLUSION: The method of decomposing the optimization problem into several simple steps is capable of rapidly, consistently, and reliably designing conformal treatment plans of high uniformity. Operator dependence has been significantly reduced. We are adapting the method for other anatomic sites.

Brachytherapy↗