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Rex Cheung

Publications and source records attributed to Rex Cheung.

23 records · Page 2Linked to original sources

Dose-volume response analyses of late rectal bleeding after radiotherapy for prostate cancer.

PURPOSE: To compare the fits of various normal tissue complication probability (NTCP) models to a common set of late rectal toxicity data, with the aim of identifying the best model for predicting late rectal injury after irradiation. METHODS AND MATERIALS: Late toxicity data from 128 prostate cancer patients treated on protocol with three-dimensional conformal radiotherapy at The University of Texas M.D. Anderson Cancer Center (UTMDACC) were analyzed. The dose-volume histogram for total rectal volume, including contents, was obtained for each patient, and the presence or absence of Grade 2 or worse rectal bleeding within 2 years of treatment was scored. Five different NTCP models were fitted to the data using maximum likelihood analysis: the Lyman model, the mean dose model, a parallel architecture model, and models based on either a cutoff dose or a cutoff volume. RESULTS: All five of the NTCP models considered provided very similar fits to the UTMDACC rectal bleeding data. In particular, none of the more highly parameterized models (the four-parameter parallel model, three-parameter Lyman model, or three-parameter cutoff dose and volume models) provided a better fit than the simplest of the models, the two-parameter NTCP model describing rectal bleeding as a probit function of mean dose to rectum. CONCLUSION: No dose-volume response model has yet been identified that provides a better description of the UTMDACC rectal toxicity data than the mean dose model. Because this model has relatively low predictive accuracy, the need to identify a better model remains.

Dose-Response Relationship, Radiation↗

Characterization of rectal normal tissue complication probability after high-dose external beam radiotherapy for prostate cancer.

PURPOSE: Conformal radiotherapy (RT) has allowed radiation dose escalation to improve the outcome of prostate cancer. With higher doses, concern exists that rectal injury may increase. This study analyzed the utility and limitations of the widely used Lyman-Kutcher- Burman (LKB) normal tissue complication probability model in projecting the hazards of rectal complication with high-dose RT. METHODS AND MATERIALS: A total of 128 patients were included in this study. These patients were treated with three-dimensional conformal RT alone at the University of Texas M.D. Anderson Cancer Center between 1992 and 1999. Patients were treated to 46 Gy with a four-field box technique followed by a six-field arrangement to boost the total dose to 78 Gy. All doses were delivered at 2 Gy/fraction to the isocenter. The minimal follow-up was 2 years. The end point for analysis was Grade 2 or worse rectal bleeding by 2 years. The LKB model was fitted to the data using the maximal likelihood method. RESULTS: Of the 128 patients, 29 experienced Grade 2 or worse rectal bleeding by 2 years. For the entire cohort, the parameters obtained from the fit of the LKB model were as follows: the volume factor was n = 3.91 (95% confidence interval [CI] 0.031 to infinity ), dose associated with 50% chance of complication for uniform whole rectal irradiation [TD50(1)] was 53.6 Gy (95% CI 50.0-75.1), and a determinant of the steepness of the dose-response curve, (m), was 0.156 (95% CI 0.036-0.271). A statistically significant difference was found in the rate of postradiation rectal bleeding in patients with hemorrhoids vs. those without hemorrhoids. The parameters obtained for the patients without hemorrhoids were as follows: n = 0.746 (95% CI 0.026 to infinity ), TD50(1) 56.7 Gy (95% CI 49.9-75.2), and m 0.092 (95% CI 0.019-0.189). CONCLUSION: Our analysis suggests a dose response for rectal bleeding probability along with a volume effect. We found that the LKB model might have limited utility in determining a large volume effect. We further suggest that LKB model should be used with caution in clinical practice.

Dose-Response Relationship, Radiation↗

Dose-response for biochemical control among high-risk prostate cancer patients after external beam radiotherapy.

INTRODUCTION: The literature on dose-response characteristics of high-risk prostate cancer has been scarce in this era, when these patients are treated with hormone therapy along with radiotherapy. In this study, we estimated the dose-response of prostate-specific antigen (PSA) control probability in high-risk prostate cancer patients treated with radiotherapy alone. METHODS AND MATERIALS: The data set contains information on 363 high-risk prostate cancer patients who were treated with external beam radiotherapy without hormonal treatment between February 1987 and September 1998. These patients have one or more of the following adverse prognostic features: digital rectal examination stage > or =cT3, PSA >20 ng/mL, and biopsy Gleason score > or =8. These patients had biopsy-proven adenocarcinoma of prostate and were staged according to the 1992 AJCC staging system that was based on digital rectal examination. The logistic model was fitted to the data at various time points after treatment, and the dose-response parameters were estimated. RESULTS: The dose required to have 50% tumor control, TCD50 (95% confidence interval), for high-risk patients is 75.5 (range: 70.7-80.2) Gy. The gamma 50 (95% confidence interval) is 1.7 (range: 0.7-2.7) around 75.5 Gy. Recursive partitioning analysis based on the null Martingale residuals identifies two subgroups within the high-risk group. The TCD50 estimates of the two subgroups (PSA < or = vs. >20 ng/mL) differ by 15 Gy at 5 years. There is a dose response in both subgroups. CONCLUSION: We recognize that this study has the usual limitations of a retrospective study that includes treatment policy change that spanned a long time frame. However, our data strongly suggest a benefit of dose escalation for all the patients in the entire high-risk group. There is a steep dose response in PSA control probability around a modern dose of 78 Gy. A 5-Gy dose increase beyond 78 Gy may improve PSA control by about 10%.

Aged↗

Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model.

We compared light-induced fluorescence (LIF) to nominal injected drug dose for predicting the depth of necrosis response to photodynamic therapy (PDT) in a murine tumor model. Mice were implanted with radiation-induced fibrosarcoma (RIF) and were injected with 0, 5, or 10 mg/kg Photofrin. 630-nm light (30 J/cm(2), 75 mW/cm(2)) was delivered to the tumor after 24 hours. Fluorescence emission (lambda(excitation)=545 nm, lambda( emission)=628 nm) from the tumor was measured. The LIF data had less scatter than injected drug dose, and was found to be at least as good as an injected drug dose for predicting the depth of necrosis after PDT. Our observations provide further evidence that fluorescence spectroscopy can be used to quantify tissue photosensitizer uptake and to predict PDT tissue damage.

Animals↗

In vivo reflectance measurement of optical properties, blood oxygenation and motexafin lutetium uptake in canine large bowels, kidneys and prostates.

Motexafin lutetium (MLu) is a second-generation photosensitizer for photodynamic therapy (PDT) of cancer. We have developed and applied a diffuse optical reflectance spectrometer for in vivo measurement of MLu uptake, optical properties, haemoglobin concentration and haemoglobin oxygen saturation in normal canine large bowels, kidneys and prostates. The probe consists of a broadband fibre-optic-coupled light source and detector fibres placed at various distances from the source fibre to collect reflected light. An analysis based on the diffusion approximation of the photon transport equation was used to recover tissue optical properties from the reflectance measurements. The instrumentation and analysis methods were validated using measurements from homogeneous, highly scattering phantoms with known MLu concentrations. The same techniques were then used to estimate chromophore concentrations of normal canine large bowels, kidneys and prostates. We estimated (mean (standard deviation)) total haemoglobin concentrations of 119 (25), 340 (92) and 51 (11) microM in the large bowels, kidneys and prostates of four dogs, respectively; tissue blood oxygen saturations in these same organs were 75 (15), 76 (21) and 74 (16) per cent, respectively. Tissue MLu concentrations (mg l(-1)) were estimated from data taken 3.5 h after injection of a 2 mg kg(-1) injected dose; data from three dogs gave concentrations of 2.4 (0.4) in large bowels, 6.8 (1.3) in kidneys and 2.2 (1.1) in prostates. The reduced scattering coefficients, mu's, estimated for large bowels, kidneys and prostates at 730 nm were, respectively: 10.1 (1.3), 19.6 (4.0) and 12.7 (0.6) cm(-1). We observed significant variability in MLu uptake, tissue scattering and haemoglobin concentration between organs and even between the same organ in different dogs. This class of in situ optical property measurement may be desirable to individualize PDT drug and light delivery.

Algorithms↗