Rex Cheung

QUANTIFICATION OF PROSTATE AND SEMINAL VESICLE INTERFRACTION VARIATION DURING IMRT

PURPOSE To quantify the interfraction variability in prostate and seminal vesicle (SV) positions during a course of intensity-modulated radiotherapy (IMRT) using an integrated computed tomography (CT)-linear accelerator system and to assess the impact of rectal and bladder volume changes. METHODS AND MATERIALS We studied 15 patients who had undergone IMRT for prostate carcinoma. Patients had one pretreatment planning CT scan followed by three in-room CT scans per week using a CT-on-rails system. The prostate, bladder, rectum, and pelvic bony anatomy were contoured in 369 CT scans. Using the planning CT scan as a reference, the volumetric and positional changes were analyzed in the subsequent CT scans. RESULTS For all 15 patients, the mean systematic internal prostate and SV variation was 0.1 +/- 4.1 mm and 1.2 +/- 7.3 mm in the anteroposterior axis, -0.5 +/- 2.9 mm and -0.7 +/- 4.5 mm in the superoinferior axis, and 0.2 +/- 0.9 mm and -0.9 +/- 1.9 mm in the lateral axis, respectively. The mean magnitude of the three-dimensional displacement vector was 4.6 +/- 3.5 mm for the prostate and 7.6 +/- 4.7 mm for the SVs. The rectal and bladder volume changes during treatment correlated with the anterior and superior displacement of the prostate and SVs. CONCLUSION The dominant prostate and SV variations occurred in the anteroposterior and superoinferior directions. The systematic prostate and SV variation between the treatment planning CT and daily therapy as a result of the rectal and bladder volume changes emphasizes the need for daily directed target localization and/or immobilization techniques.

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%.

Radiotherapy sensitization by tumor-specific TRAIL gene targeting improves survival of mice bearing human non-small cell lung cancer

Purpose: To sensitize non–small cell lung cancer (NSCLC) to radiotherapy by tumor-specific delivery of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) gene. Experimental Design: The TRAIL was delivered to human NSCLC cell lines and normal human bronchial epithelial cells by the replication-defective adenoviral vector Ad/TRAIL-F/RGD using a tumor-specific human telomerase reverse transcriptase promoter. Cancer growth was studied using 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt and clonogenic assays. Activation of the apoptosis pathway was analyzed in a Western blot and sub-G1 DNA accumulation. A xenograft mouse lung cancer model was treated by intratumoral injections of Ad/TRAIL-F/RGD and local radiotherapy; the other groups received one of these treatments alone or a control agent. Apoptosis and TRAIL expression in tumors were also analyzed. Results: Ad/TRAIL-F/RGD specifically targets human NSCLC cells without significant effect in normal human bronchial epithelial cells. The combination of Ad/TRAIL-F/RGD and radiotherapy significantly improved cell-killing effect in all NSCLC cell lines tested (P < 0.05). Expression of TRAIL showed a dose-dependent relationship with Ad/TRAIL-F/RGD, and radiation seemed to increase TRAIL expression. Activation of the apoptosis by TRAIL and radiation was shown by activation of caspase-9, caspase-8, caspase-3, and poly(ADP-ribose) polymerase and increased DNA sub-G1 accumulation. The combination of TRAIL and radiotherapy significantly increased apoptosis in vivo, inhibited tumor growth, and prolonged mean survival in mice bearing human NSCLC to 43.7 days compared with 23.7 days (TRAIL only) and 16.5 days (radiotherapy only; P < 0.05). Conclusions: The combination of Ad/TRAIL-F/RGD and radiotherapy significantly improved therapeutic efficacy in suppressing NSCLC tumor growth and prolonging survival. Ad/TRAIL-F/RGD may improve the therapeutic ratio of radiotherapy in NSCLC.

Comparison of treatment volumes and techniques in prostate cancer radiation therapy

Objective:To compare dose-volume histograms (DVHs) for 3 target volumes (group 1, prostate + seminal vesicles + pelvic lymph nodes; group 2, prostate + seminal vesicles; group 3, prostate only) to determine the difference in dose to normal structures (rectum, bladder, and femoral heads) while controlling for target dose using 3-dimensional conformal radiation therapy (3DCRT) versus intensity modulated radiation therapy (IMRT). Methods:Ten patients with localized prostate cancer were randomly selected. 3DCRT and IMRT planning were done to deliver 75.6 Gy to the prostate, 50.4 Gy to the pelvic nodes, and 55.8 Gy to the seminal vesicles at a standard fractionation of 1.8 Gy. An additional plan delivering 75.6 Gy to the seminal vesicles using IMRT was run. DVHs were compared for 3DCRT and IMRT. Results:In all 3 groups, the percent rectum receiving ≥70 Gy, ≥60 Gy, and ≥40 Gy was significantly less for IMRT than for 3DCRT. Increasing target volumes, as necessary for pelvic nodal irradiation, overall did not result in higher rectal doses for IMRT. With 3DCRT, however, larger target volumes did increase the amount of rectum irradiated. Similar results were obtained for the femoral heads whereas results for the bladder were mixed. Conclusion:When compared with 3DCRT, IMRT delivered equivalent or higher doses to the target volume with greater sparing of critical organs. Because dose-volume parameters have been shown to relate to toxicity, IMRT would appear to be the favored technique for prostate cancer radiation, particularly with regard to nodal treatment.

Using a priori structural information from magnetic resonance imaging to investigate the feasibility of prostate diffuse optical tomography and spectroscopy: A simulation study

Implementation of diffuse optical tomography (DOT) for prostate cancer is challenging because the prostate is a deep-seated organ. We investigated whether diffuse optical tomography (DOT) and spectroscopy could be applied to monitor the physiology of prostate cancer using a small probe that could be placed endorectally. We manually segmented the prostate, the intraprostatic tumor, and the rectum using data from endorectal magnetic resonance imaging. These structures were reconstructed and meshed with tetrahedral finite elements in three dimensions. A 2 x 4 cm probe that has ten sources and 52 detectors were placed to face the anterior wall of the rectum in our simulation. Optical properties of the organs were obtained from the literature in the near infrared regime. Diffusion approximation was used to simulate photon migration with finite element method. Five wavelengths were used to simulate tissue absorption with realistic water, oxy- and deoxyhaemoglobin concentrations in the prostate. We combined a global search based on genetic algorithm with gradient-driven local search methods to fit the simulated data. Our results suggest that the optical properties and the concentrations of the chromophores of the prostate and the prostate cancer can be reliably recovered from the measurements using an endorectal probe. Prostate DOT is worth further investigation for clinical application.

Intensity-Modulated Radiation Therapy with Noncoplanar Beams for Treatment of Prostate Cancer in Patients with Bilateral Hip Prosthesis-A Case Study

Megavoltage photon intensity-modulated radiation therapy (IMRT) is typically used in the treatment of prostate cancer at our institution. Approximately 1% to 2% of patients with prostate cancer have hip prostheses. The presence of the prosthesis usually complicates the planning process because of dose perturbation around the prosthesis, radiation attenuation through the prosthesis, and the introduction of computed tomography artifacts in the planning volume. In addition, hip prostheses are typically made of materials of high atomic number, which add uncertainty to the dosimetry of the prostate and critical organs in the planning volume. When the prosthesis is bilateral, treatment planning is further complicated because only a limited number of beam angles can be used to avoid the prostheses. In this case study, we will report the observed advantages of using noncoplanar beams in the delivery of IMRT to a prostate cancer patient with bilateral hip prostheses. The treatment was planned for 75.6 Gy using a 7-field coplanar approach and a noncoplanar arrangement, with all fields avoiding entrance though the prostheses. Our results indicate that, compared with the coplanar plan, the noncoplanar plan delivers the prescribed dose to the target with a slightly better conformality and sparing of rectal tissue versus the coplanar plan.

A volumetric trend analysis of the prostate and seminal vesicles during a course of intensity-modulated radiation therapy.

Purpose:The purpose of this study was to evaluate the volumetric changes of the prostate and seminal vesicles (SV) during a definitive course of intensity-modulated radiation therapy using a combined computed tomography (CT)-linear accelerator system. Methods and Materials:Fifteen patients were enrolled in this IRB-approved prospective study. The treatment plan was designed to deliver a total dose of 75.6 Gy over 42 fractions to 98% of the planning target volume. In-room CT scans were acquired using a CT-on-rails system 3 times weekly just before daily treatment throughout the course of radiation therapy. Rates of volume change over time for the prostate and SV were calculated using linear regression analysis. Results:Fifteen patients had a total of 369 CT scans during the study. For 53% of patients (N = 8), there was a statistically significant decrease in prostate volume over time (range, 0.05–0.47 mL/d or 0.7%–3.5% per week). The median volume reduction was −11.5% (4.9 mL) at the end of the treatment. There was no significant change in the volume of the SV during the course of treatment. The decrease in prostate volume was significantly correlated with the initial volume of the prostate, with larger glands shrinking more during treatment (P = 0.001). Conclusion:Patients with enlarged prostates may experience volumetric reduction in their gland size during a protracted course of radiation therapy. However, the magnitude of the volume reduction is relatively small. In the current era of dose escalation, future studies with adaptive radiation therapy strategy may be appropriate to minimize radiation exposure to normal tissues.

DAILY BONE ALIGNMENT WITH LIMITED REPEAT CT CORRECTION RIVALS DAILY ULTRASOUND ALIGNMENT FOR PROSTATE RADIOTHERAPY

PURPOSE To compare the effectiveness of daily ultrasound (US)- and computed tomography (CT)-guided alignments with an off-line correction protocol using daily bone alignment plus a correction factor for systematic internal prostate displacement (CF(ID)). METHODS AND MATERIALS Ten prostate cancer patients underwent CT scans three times weekly using an integrated CT-linear accelerator system, followed by alignment using US for daily radiotherapy. Intensity-modulated radiotherapy plans were designed with our current clinical margins. The treatment plan was copied onto the repeat CT images and aligned using several methods: (1) bone alignment plus CF(ID) after three off-line CT scans (bone+3CT), (2) bone alignment plus CF(ID) after six off-line CT scans (bone+6CT), (3) US alignment, and (4) CT alignment. The accuracy of the repeated US and CT measurements to determine the CF(ID) was compared. The target dosimetric effect was quantified. RESULTS The CF(ID) for internal systematic prostate displacements was more accurately measured with limited repeat CT scans than with US (residual error, 0.0 +/- 0.7 mm vs. 2.0 +/- 3.2 mm). Bone+3CT, bone+6CT, and US provided equivalent prostate and seminal vesicle dose coverage, but bone+3CT and bone+6CT produced more precise daily alignments. Daily CT alignment provided the greatest target dose coverage. CONCLUSION Daily bone alignment plus CF(ID) for internal systematic prostate displacement provided better daily alignment precision and equivalent dose coverage compared with daily US alignment. The CF(ID) should be based on at least three repeat CT scans, which could be collected before the start of treatment or during the first 3 treatment days. Daily bone alignment plus CF(ID) provides another option for accurate prostate cancer patient positioning.

SU-FF-J-40: Comparison of Prostate Implanted Fiducials with CT and Ultrasound for Prostate Target Localization: Initial Results

Purpose: To compare prostate localization methods of implanted fiducials, CT‐guided, and ultrasound‐guided (US) techniques. Method and Materials: Data were collected from an on‐going institutional review board approved protocol for comparing different target localization techniques for image‐guided prostate cancerradiotherapy. The protocol is designed to have CT scans with an in‐room CT‐on‐rails three times a week; US‐guided localization twice a week for the initial two weeks, then weekly; and orthogonal electronic portal imaging for fiducial measurements daily. Patients will have three gold seed implanted fiducials for prostate localization. The NOMOS BAT system and MedTecs Acculoc software are used for US and fiducial localization, respectively. All shifts reported by the three methods are relative to the same daily reference point set on patients skin during the entire imaging session. The differences in the three methods were compared and the mean and standard deviation were computed in each of the orthogonal shifted positions: anterior‐posterior (AP), superior‐inferior (SI), and laterals (RL). Correlation coefficients were determined relative to the CT localization method. Results: We report the results for the first patient who had just completed treatment. The mean differences (one standard deviation) (in cm) between the implanted fiducials and CT were −0.03 (0.18), 0.0 (0.12), −0.03 (0.15), while US and CT were 0.14 (0.68), −0.21 (0.68), and 0.32 (0.28), in AP, SI, and RL directions, respectively. The Spearmans correlation coefficients relative to the CT registration were 0.83, 0.60, and 0.81 for the implanted fiducial method (p 0.05 for AP and SI directions). Note that simultaneous measurements were 22 for CT and fiducials while only 9 for CT and US.Conclusions: Implanted fiducial registration correlates better than the US relative to the CT‐guided approach. More patients are needed to make a firm conclusion.

WE‐E‐ValA‐02: Dosimetric Comparison of the No Action Level Alignment Protocol with Daily Alignment Techniques for Prostate Cancer

Purpose: To compare the effectiveness of two off‐line “No‐Action‐Level” (NAL) correction protocols with daily image‐guided alignments using bony registration (simulating electronic portal image alignment), ultrasound, and CT for direct prostate target localization. Method and Materials: Ten prostate patients received 3 CT scans per week using an integrated CTLINAC system immediately prior to radiotherapy (243 CT scans total). A clinical treatment plan was designed on the planning CTimage using current clinical margins and copied onto the daily CTimages. Two NAL protocols, based on CT measurements of the internal prostate shift relative to bony anatomy, were simulated for correcting the predicted internal systematic prostate shifts after 1 week or after 2 weeks of treatment. The NAL protocols were compared to three daily alignment methods, which simulated pelvic bone alignment, ultrasound alignment, and CT alignment. The dosimetric impact on target coverage for each scenario was reported. Reducing the planning margins to 3mm was also evaluated. Results: Daily CT scans are more accurate than daily ultrasound measurements for determining the prostate systematic positional shift, particularly in the anterior/posterior direction. The average minimum prostate dose was greatest with CT alignment (75.8Gy, p<=0.028), then with the two NAL protocols (both 74.Gy, p<=0.017), followed by ultrasound alignment (73.2Gy) and bone alignment (70.2Gy). For plans with 3mm margins, the average minimum dose was greatest with CT alignment (75.1Gy, p<=0.007), then with the two adaptive alignments (71.4Gy and 70.8Gy respectively, p<=0.022), followed by ultrasound alignment (68.4Gy) and bone alignment (63.9Gy). Conclusions: An off‐line NAL correction protocol for reducing systematic internal target shifts proved to be effective when performed after only one treatment week. The target dosimetric coverage from the NAL protocol was as good as daily ultrasound alignments but not as great as daily CT alignments. Using a 3mm planning margin exacerbated the differences in target coverage.