Biomedical subjects

Rex Cheung

Publications and source records attributed to Rex Cheung.

At least 19 recordsLinked to original sources

PubMed2006

Dosimetric comparison of four target alignment methods for prostate cancer radiotherapy.

PURPOSE: The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. RESULTS: Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. CONCLUSIONS: Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate.

Algorithms↗

PubMed2006

First-year PSA kinetics and minima after prostate cancer radiotherapy are predictive of overall survival.

PURPOSE: We analyzed whether first-year prostate-specific antigen (PSA) kinetics and minima are predictive of overall survival (OS). METHODS AND MATERIALS: The data set contained 1,174 patients treated with external beam radiotherapy (RT) from 1987 to 2001. The relative rate of change (lambda) in post-RT PSA values during the first year (13.5 months) was computed using regression analysis of ln(PSA) vs. time. We also computed the PSA minimum (mPSA) reached during the same period. Recursive partitioning analysis was used to identify the relevant cutpoints for the factors being investigated for its association with survival: age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT, and 1-year PSA minimum. For each of the other factors stage, Gleason score and risk group, all possible cutpoints were considered in the multivariate analyses. Significant factors were considered in the multivariate analyses to identify independent predictors for overall survival. RESULTS: The median value of lambda was -1.0 years(-1) (range, -11.0-5.1 years(-1)). The 1-year minimum had a median of 0.8 ng/mL (range, 0.01-30.9 ng/mL). Recursive partitioning analysis and Cox proportional hazards analyses identified the following pretreatment or treatment factors adversely related to OS: age, Gleason score, stage, and dose. First-year mPSA > or = 4 ng/mL and lambda > 0 were post-RT independent prognostic factors for worse OS. CONCLUSION: First-year post-RT PSA kinetics and minima are early response parameters predictive of overall survival for prostate cancer patients. These factors may be useful in selecting patients for early salvage therapy.

Adult↗

PubMed2006

Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma.

PURPOSE: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). METHODS AND MATERIALS: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. RESULTS: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). CONCLUSIONS: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival.

Adenocarcinoma↗

PubMed2005

Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy.

PURPOSE: To determine whether prostate-specific antigen (PSA) doubling time predicts clinical outcomes in patients with prostate cancer that has been treated with combined radiation and hormone therapy. METHODS AND MATERIALS: We reviewed the medical records of 621 men with nonmetastatic prostate cancer treated with radiation therapy and hormone therapy between 1989 and 2003. "Any" clinical failure was defined as any distant, nodal, or local failure, or the use of salvage therapy. "True" clinical failure was defined as any distant, nodal, or local failure. PSA doubling time was calculated by using the log PSA values from patients with a PSA failure as defined by the American Society of Therapeutic Radiology Oncology consensus statement. One hundred thirty-seven men were at intermediate risk for PSA failure (as determined by T2b, Gleason score of 7, or PSA 10.1-0 ng/mL) and 484 men were at high risk for failure (T2c-4; Gleason 8-10; or PSA >20 ng/mL). Pretreatment PSA value, Gleason score, tumor stage, timing and duration of hormone therapy, radiation therapy dose, and PSA doubling time were analyzed for any associations with time to clinical failure by using Cox regression analysis. Estimates of survival were calculated by using the Kaplan-Meier method. Pairwise comparisons were made by using the log-rank test. RESULTS: Sixty-two men experienced any clinical failure, and 22 men experienced true clinical failure. Multivariate analysis revealed that pretreatment PSA (p = 0.013), Gleason score (p = 0.0019), and a PSA doubling time (PSADT) < or =8 months (p < 0.001) were independently associated with time to any clinical failure. Tumor stage, hormone therapy timing, hormone therapy duration, and radiation therapy dose were not statistically significant on multivariate or univariate analysis. Only hormone therapy duration (p = 0.008) and PSADT < or =8 months (<0.001) were significantly associated with time to true clinical failure. The estimated 5-year rate of any clinical failure was 9.4% for men with a PSADT >8 months and 60.4% for men with a PSA doubling time < or =8 months (p < 0.001). The estimated 5-year rate of true clinical failure was 6.5% for men with a PSADT >8 months and 68.5% for men with a PSADT < or =8 months (p < 0.001). Lower radiation dose was the only significant predictor of PSADT < or =8 months on multivariate regression analysis. The estimated 6-year overall survival rate after PSA failure was 79.1% for men with a PSADT >8 months and 29.7% for men with a PSADT < or =8 months. The median overall survival time for patients with a PSADT >8 months was not reached in this study. The median overall survival time for patients with a PSADT < or =8 months was 61.8 months (p = 0.015). CONCLUSION: In men with prostate cancer that has been treated with combined hormone and radiation therapy, a posttreatment PSADT of < or =8 months is associated with worse clinical outcomes and may be an early surrogate marker for decreased survival. These patients should be considered for more aggressive salvage therapy protocols.

Aged↗

PubMed2005

Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy.

BACKGROUND: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. PATIENTS AND METHODS: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. RESULTS: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA < or = 0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. CONCLUSION: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal treatment. We further suggest that salvage radiotherapy should be given early when the PSA is still low.

Adult↗

PubMed2005

Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy.

PURPOSE: To retrospectively test the hypothesis that rectal distension on the planning computed tomography (CT) scan is associated with an increased risk of biochemical and local failure among patients irradiated for prostate carcinoma when a daily repositioning technique based on direct prostate-organ localization is not used. METHODS AND MATERIALS: This study included 127 patients who received definitive three-dimensional conformal radiotherapy for prostate cancer to a total dose of 78 Gy at The University of Texas M. D. Anderson Cancer Center. Rectal distension was assessed by calculation of the average cross-sectional rectal area (CSA; defined as the rectal volume divided by length) and measuring three rectal diameters on the planning CT. The impact of rectal distension on biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or greater late rectal bleeding was assessed. RESULTS: The incidence of biochemical failure was significantly higher among patients with distended rectums (CSA >11.2 cm(2)) on the planning CT scan (p = 0.0009, log-rank test). Multivariate analysis indicates that rectal distension and high-risk disease are independent risk factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to 9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The probability of residual tumor without evidence of radiation treatment (as scored by the pathologist) increased significantly with rectal distension (p = 0.010, logistic analysis), and a lower incidence of Grade 2 or greater late rectal bleeding within 2 years was simultaneously observed with higher CSA values (p = 0.031, logistic analysis). CONCLUSIONS: We found strong evidence that rectal distension on the treatment-planning CT scan decreased the probability of biochemical control, local control, and rectal toxicity in patients who were treated without daily image-guided prostate localization, presumably because of geographic misses. Therefore, an empty rectum is warranted at the time of simulation. These results also emphasize the need for image-guided radiotherapy to improve local control in irradiating prostate cancer.

Aged↗

PubMed2005

Validation of an accelerated 'demons' algorithm for deformable image registration in radiation therapy.

A greyscale-based fully automatic deformable image registration algorithm, originally known as the 'demons' algorithm, was implemented for CT image-guided radiotherapy. We accelerated the algorithm by introducing an 'active force' along with an adaptive force strength adjustment during the iterative process. These improvements led to a 40% speed improvement over the original algorithm and a high tolerance of large organ deformations. We used three methods to evaluate the accuracy of the algorithm. First, we created a set of mathematical transformations for a series of patient's CT images. This provides a 'ground truth' solution for quantitatively validating the deformable image registration algorithm. Second, we used a physically deformable pelvic phantom, which can measure deformed objects under different conditions. The results of these two tests allowed us to quantify the accuracy of the deformable registration. Validation results showed that more than 96% of the voxels were within 2 mm of their intended shifts for a prostate and a head-and-neck patient case. The mean errors and standard deviations were 0.5 mm+/-1.5 mm and 0.2 mm+/-0.6 mm, respectively. Using the deformable pelvis phantom, the result showed a tracking accuracy of better than 1.5 mm for 23 seeds implanted in a phantom prostate that was deformed by inflation of a rectal balloon. Third, physician-drawn contours outlining the tumour volumes and certain anatomical structures in the original CT images were deformed along with the CT images acquired during subsequent treatments or during a different respiratory phase for a lung cancer case. Visual inspection of the positions and shapes of these deformed contours agreed well with human judgment. Together, these results suggest that the accelerated demons algorithm has significant potential for delineating and tracking doses in targets and critical structures during CT-guided radiotherapy.

Algorithms↗

PubMed2005

An automatic CT-guided adaptive radiation therapy technique by online modification of multileaf collimator leaf positions for prostate cancer.

PURPOSE: To propose and evaluate online adaptive radiation therapy (ART) using in-room computed tomography (CT) imaging that detects changes in the target position and shape of the prostate and seminal vesicles (SVs) and then automatically modifies the multileaf collimator (MLC) leaf pairs in a slice-by-slice fashion. METHODS AND MATERIALS: For intensity-modulated radiation therapy (IMRT) using a coplanar beam arrangement, each MLC leaf pair projects onto a specific anatomic slice. The proposed strategy assumes that shape deformation is a function of only the superior-inferior (SI) position. That is, there is no shape change within a CT slice, but each slice can be displaced in the anteroposterior (AP) or right-left (RL) direction relative to adjacent slices. First, global shifts (in SI, AP, and RL directions) were calculated by three-dimensional (3D) registration of the bulk of the prostate in the treatment planning CT images with the daily CT images taken immediately before treatment. Local shifts in the AP direction were then found using slice-by-slice registration, in which the CT slices were individually registered. The translational shift within a slice could then be projected to a translational shift in the position of the corresponding MLC leaf pair for each treatment segment for each gantry angle. Global shifts in the SI direction were accounted for by moving the open portal superiorly or inferiorly by an integral number of leaf pairs. The proposed slice-by-slice registration technique was tested by using daily CT images from 46 CT image sets (23 each from 2 patients) taken before the standard delivery of IMRT for prostate cancer. A dosimetric evaluation was carried out by using an 8-field IMRT plan. RESULTS: The shifts and shape change of the prostate and SVs could be separated into 3D global shifts in the RL, AP, and SI directions, plus local shifts in the AP direction, which were different for each CT slice. The MLC leaf positions were successfully modified to compensate for these global shifts and local shape variations. The ART method improved geometric coverage of the prostate and SVs compared with the couch-shift method, particularly for the superior part of the prostate and all the SVs, for which the interfraction shape change was the largest. The dosimetric comparison showed that the ART method covered the target better and reduced the rectal dose more than a simple couch-translation method. CONCLUSIONS: ART corrected for interfraction changes in the position and shape of the prostate and SVs and gave dose distributions that were considerably closer to the planned dose distributions than could be achieved with simple alignment strategies that neglect shape change. The ART proposed in this investigation requires neither contouring of the daily CT images nor extensive calculations; therefore, it may prove to be an effective and clinically practical solution to the problem of interfraction shape changes.

Algorithms↗

PubMed2005

Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy.

PURPOSE: In this era of dose escalation, the benefit of higher radiation doses for low-risk prostate cancer remains controversial. For intermediate-risk patients, the data suggest a benefit from higher doses. However, the quantitative characterization of the benefit for these patients is scarce. We investigated the radiation dose-response relation of tumor control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. We also investigated the differences in the dose-response characteristics using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition vs. an alternative biochemical failure definition. METHODS AND MATERIALS: This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment between 1987 and 1998. The low-risk patients had 1992 American Joint Committee on Cancer Stage T2a or less disease as determined by digital rectal examination, prostate-specific antigen (PSA) levels of < or =10 ng/mL, and biopsy Gleason scores of < or =6. The intermediate-risk patients had one or more of the following: Stage T2b-c, PSA level of < or =20 ng/mL but >10 ng/mL, and/or Gleason score of 7, without any of the following high-risk features: Stage T3 or greater, PSA >20 ng/mL, or Gleason score > or =8. The logistic models were fitted to the data at varying points after treatment, and the dose-response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises, with the time to failure backdated to the mid-point between the nadir and the first rise. The second biochemical failure definition used was a PSA rise of > or =2 ng/mL above the current PSA nadir (CN + 2). The failure date was defined as the time at which the event occurred. Local, nodal, and distant relapses and the use of salvage hormonal therapy were also failures. RESULTS: On the basis of the ASTRO definition, at 5 years after radiotherapy, the dose required for 50% tumor control (TCD(50)) for low-risk patients was 57.3 Gy (95% confidence interval [CI], 47.6-67.0). The gamma50 was 1.4 (95% CI, -0.1 to 2.9) around 57 Gy. A statistically significant dose-response relation was found using the ASTRO definition. However, no dose-response relation was noted using the CN + 2 definition for these low-risk patients. For the intermediate-risk patients, using the ASTRO definition, the TCD(50) was 67.5 Gy (95% CI, 65.5-69.5) Gy and the gamma50 was 2.2 (95% CI, 1.1-3.2) around TCD(50). Using the CN + 2 definition, the TCD(50) was 57.8 Gy (95% CI, 49.8-65.9) and the gamma50 was 1.4 (95% CI, 0.2-2.5). Recursive partitioning analysis identified two subgroups within the low-risk group, as well as the intermediate-risk group: PSA level <7.5 vs. > or =7.5 ng/mL. Most of the benefit from the higher doses for the low- and intermediate-risk group was derived from the patients with the higher PSA values. For the low-risk group, the dose-response curves essentially plateaued at 78 Gy. CONCLUSION: A dose-response relation was found using the ASTRO definition for low-risk prostate cancer. However, we found only marginal or no dose-response relation when the CN + 2 definition was used. Most of the benefit from the higher doses derived from low-risk patients with higher PSA levels. In all cases, little projected gain appears to exist at doses >78 Gy for these patients. A dose-response relation was noted for the intermediate-risk patients using either the CN + 2 or ASTRO definition. Most of the benefit from the higher doses also derived from the intermediate-risk patients with higher PSA levels. Some room for improvement appears to exist with additional dose increases in this group.

Aged↗

PubMed2005

Implementation and validation of a three-dimensional deformable registration algorithm for targeted prostate cancer radiotherapy.

PURPOSE: Daily prostate deformation hinders accurate calculation of dose, especially to intraprostatic targets. We implemented a three-dimensional deformable registration algorithm to aid dose tracking for targeted prostate radiotherapy. METHODS AND MATERIALS: The algorithm registers two computed tomography (CT) scans by iteratively minimizing their differences in image intensity. For validation, we measured the accuracy in registering (a) a pelvic CT set to its mathematically deformed counterpart, (b) CT scans of a deformable pelvic phantom with and without an endorectal balloon inflated, to simulate intraprostatic targets, 23 CT-opaque seeds were embedded in the prostate, and (c) two pelvic CT scans of a patient obtained on 2 separate days. RESULTS: The mean (SD) error in registering the pelvic CT set to its transformed set was 0.5 mm (1.5), with correlation coefficient improvement from 0.626 to 0.991. Using the deformable pelvic phantom, the correlation coefficient improved from 0.543 to 0.816 after registration. The mean (SD) error in tracking the intraprostatic seeds was 0.8 mm (0.5). The correlation coefficient improved from 0.610 to 0.944 after registration of the two patient CT sets. CONCLUSION: The algorithm had an accuracy of about 1 mm. It could be used for optimizing dose calculation and delivery for prostate radiotherapy.

Algorithms↗

PubMed2005

Assessing the impact of an alternative biochemical failure definition on radiation dose response for high-risk prostate cancer treated with external beam radiotherapy.

PURPOSE: The American Society for Therapeutic Radiology and Oncology (ASTRO) biochemical failure definition has recently been compared with various alternative definitions. We assessed the effect of using an alternative failure definition on the dose-response characteristics of high-risk prostate cancer treated with radiotherapy alone. METHODS AND MATERIALS: This study included 363 high-risk prostate cancer patients treated with external beam radiotherapy alone from 1987 to 1999. These patients have one or more of the following: 1992 American Joint Committee on Cancer (AJCC) digital rectal examination (DRE) stage > or = cT3, prostate-specific antigen (PSA) > 20 ng/mL, and/or biopsy Gleason score > or = 8. We previously reported the dose response based on the ASTRO definition for these patients. In this study, a biochemical failure is defined as a PSA rise > or = 2 ng/mL above the current nadir PSA (CN + 2). The failure date is defined as the time at which the event occurred (i.e., the call date). RESULTS: Using CN + 2, the tumor control probability (TCP) continues to decrease with time as opposed to reaching a plateau as with the ASTRO definition. At 5 years, TCD50 (95% CI), the dose to achieve 50% tumor control, for high-risk prostate cancer, is 70.4 (68.0-72.9) Gy using CN + 2 [ASTRO: 75.5 (70.7-80.2) Gy]. The relative slope, gamma50 (95% CI) is 1.8 (0.8-2.8) [ASTRO: 1.7 (0.7-2.7)]. Recursive partitioning again identified two subgroups: PSA < vs. > or = 13 ng/mL (ASTRO: PSA < or = vs. > 20 ng/mL). The difference in TCD50 between the two subgroups is about 20 Gy at 5 years (ASTRO: about 15 Gy at 5 years). CONCLUSION: This analysis using the CN + 2 failure definition continues to show a dose response for the high-risk group of patients. However, the dose-response characteristics differ from those estimated using the ASTRO definition. We observed that the position (TCD50) and steepness (gamma50) of the dose-response curve changed with time as long as the TCP continued to decrease. This suggests that the dose response characteristics derived from data with longer follow-up may be different from those derived with shorter follow-up using the CN + 2 or similar failure definitions which do not back-date the failure. These changes in dose-response characteristics as well as the time dependence of dose response should be noted when investigators design dose escalation trials for the high-risk prostate cancer patients.

Adenocarcinoma↗

PubMed2005

Ultrasound-based localization.

Ultrasound is a noninvasive, relatively easy, rapid, and real-time imaging technique for organ targeting for radiotherapy. Its application has been developed to a greater extent in prostate cancer than in other sites in which it has been shown to improve the accuracy of daily treatment delivery. With the move toward dose escalation and the need to maximally spare the adjacent critical structures through more conformal therapy and smaller field margins, an innovative technique for accurate and reproducible tumor targeting is mandatory. Basic ultrasound principles and organ location lend themselves well to the application of this modality in prostate cancer. Promising results using daily ultrasound-guided B-mode acquisition and targeting for patients with upper abdominal tumors suggest an area for additional trials and study. For breast cancer radiotherapy, ultrasound serves to define involved primary and nodal sites, especially in patients in whom surgical evaluation will not be the first therapeutic step.

Abdominal Neoplasms↗

PubMed2005

Is patient age a factor in the occurrence of prostate-specific antigen bounce phenomenon after external beam radiotherapy for prostate cancer?

OBJECTIVES: To evaluate the effect of patient age on the occurrence of prostate-specific antigen (PSA) "bounce" after external beam radiotherapy (EBRT) for prostate cancer. METHODS: In this study, 964 patients received EBRT alone for prostate cancer between April 1987 and January 1998 who had been followed for at least 12 months. Prostate-specific antigen values were obtained every 3 to 6 months after radiotherapy. Median overall follow-up was 48 months. Prostate-specific antigen bounce was defined as an initial increase in serum PSA of at least 0.5 ng/mL, followed by a decrease to prebounce baseline serum PSA values, all within 60 months after EBRT. Biochemical failure was defined as three consecutive increases in posttreatment PSA concentration after achieving a nadir. Multivariate Cox regression analysis was performed to evaluate the influences of age, pretreatment PSA concentration, Gleason score (determined at biopsy), clinical T stage classification, and radiation dose on PSA bounce-free survival and biochemical disease-free survival, with P < 0.05 considered statistically significant. RESULTS: Twelve percent of the patients developed a PSA bounce. Age was not associated with the occurrence of a PSA bounce (P = 0.63), the magnitude of the PSA bounce (P = 0.90), or the duration of the PSA bounce (P = 0.39). Patients who had PSA bounce had a statistically significant higher biochemical disease-free survival than those who did not (P = 0.00004). CONCLUSIONS: In our study, age was not predictive of PSA bounce. However, younger patients with a rising PSA after radiotherapy should be followed closely for evidence of biochemical failure.

Age Factors↗

PubMed2005

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 > or =70 Gy, > or =60 Gy, and > or =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.

Dose Fractionation, Radiation↗

PubMed2004

Comparison of rectal dose-wall histogram versus dose-volume histogram for modeling the incidence of late rectal bleeding after radiotherapy.

PURPOSE: To compare the fits of normal-tissue complication probability (NTCP) models based on rectal dose-wall histograms (DWHs) vs. dose-volume histograms (DVHs) when the two are used to analyze a common set of late rectal toxicity data. METHODS AND MATERIALS: Data were analyzed from 128 prostate cancer patients treated with 3-dimensional conformal radiotherapy (3D-CRT) at The University of Texas M.D. Anderson Cancer Center (UTMDACC). The DVH for total rectal volume, including contents, was obtained for each patient from the treatment-planning system. A DWH was also computed, using the outer rectal contour plus an autogenerated inner contour that corresponds to an assumed 3-mm rectal wall thickness. The endpoint for analysis was Grade 2 or higher late rectal bleeding within 2 years of treatment; all patients had at least 2 years of follow-up. Four different NTCP models were fitted to the response data by using either the DVH or the DWH to describe the dose distribution to rectum or rectal wall, respectively. The 4 models considered were the Lyman model, the mean dose model, the parallel-architecture model, and a model based on the volume of a organ receiving more than a specified dose (the "cutoff-dose" model). RESULTS: For each of the models, the fit to the late rectal bleeding data was slightly improved when the analysis was based on the rectal DWH instead of on the DVH. In addition, the results of the cutoff dose and parallel architecture models were consistent with one another for the DWH data but not for the DVH data. For the DWH data, both models predict a 50% or higher incidence of Grade 2 or worse late rectal bleeding within 2 years if 80% or more of the rectal wall is exposed to doses greater than 32 Gy. A 50% or higher incidence of rectal bleeding is also predicted if the mean dose to rectal wall exceeds 53.2 Gy. CONCLUSIONS: A consistent, although modest, improvement occurs in the fits of NTCP models to the UTMDACC 2-year late rectal bleeding data when the fit is based on the rectal dose-wall histogram instead of on the dose-volume histogram for entire rectum, including contents.

Confidence Intervals↗

PubMed2004

Erectile dysfunction and radiation dose to penile base structures: a lack of correlation.

PURPOSE: To evaluate the relationship between the dose and volume of radiation to proximal penile structures and the development of erectile dysfunction after external beam radiotherapy (RT) for localized prostate adenocarcinoma. METHODS AND MATERIALS: The study cohort comprised 28 patients who were enrolled our in-house three-dimensional conformal RT dose escalation protocol. The patients were treated to 78 Gy between 1995 and 1998. This protocol included a planned quality-of-life questionnaire to assess sexual function 2 years after completing RT. All the study patients were potent before RT. The median follow-up was 66 months (range 39-95). Penile base contents were outlined retrospectively in restored treatment plans. The dose-volume histograms (DVHs) for the corpus spongiosum (penile bulb), corpora cavernosum and crura, and total penile structure (corpus spongiosum plus corpora cavernosum and crura) were calculated. Statistical significance was defined as p < 0.05. The Bonferroni correction was used to adjust for multiple comparisons. Power calculations showed that our study sample would detect radiation- induced impotence with a very high power. We also estimated that a relatively small difference of 10-15% in the DVHs between the potent and impotent patients could be detected. RESULTS: At 2 years after RT, 10 patients (35.7%) reported new-onset erectile dysfunction and were unable to attain firm enough erections to have intercourse. Only hypertension was observed to affect erectile dysfunction after external beam RT. We found no statistically significant correlation among age, diabetes, or heavy alcohol consumption and post-RT potency. The mean radiation dose +/- standard deviation delivered to the corpus spongiosum, corpora cavernosa and crura, and total penile structure was, respectively, 42.2 +/- 8.4 Gy, 36.3 +/- 8.0 Gy, and 38.2 +/- 7.5 Gy. t test comparisons were performed between DVHs of post-RT potent and impotent patients on multiple cutpoints. No dose-volume effect was found. Analysis of the DVHs when the patients were subdivided into normotensive and hypertensive groups also showed no dose-volume response. CONCLUSION: Our analysis did not show statistically significant correlations between potency preservation and radiation dose to the proximal penis. The entire etiology of radiation- induced erectile dysfunction remains unclear and further research is needed.

Adenocarcinoma↗

PubMed2004

Evaluation of a contour-alignment technique for CT-guided prostate radiotherapy: an intra- and interobserver study.

PURPOSE: The recent introduction of integrated CT/linear accelerator systems may mean that daily CT localization can become a reality in the clinic, possibly allowing further dose escalation to the prostate while limiting unwanted doses to the rectum and bladder. However, the implementation of CT localization is currently impeded by the lack of precise and robust techniques to align the treatment plan with the daily CT images. The purpose of this study was to evaluate a manual alignment technique, in which the gross target volume contours are overlaid on the daily CT images and then shifted to match the structures visible in the images. METHODS AND MATERIALS: A total of 28 CT image sets were taken before the standard delivery of intensity-modulated radiotherapy for prostate cancer for 2 patients. Seven observers (four radiation oncologists and three medical physicists) manually shifted the gross target volume contours from the treatment plan to best match the daily CT images. One observer repeated the process 1 week later to evaluate intraobserver variations. The experiment was then repeated, but the CT images from the original treatment plan were used as a reference to reduce interobserver uncertainty when aligning the contours. The shifts in prostate position found by different observers, both with and without reference data, were evaluated using a factorial analysis of variance to determine the standard errors of measurement for the intra- and interobserver uncertainty (SEM(intra) and SEM(inter), respectively). The differences in the SEM for the two groups of observers (radiation oncologists and medical physicists), the two alignment techniques (with and without reference information), and the two patients were evaluated using the t test at 90% confidence levels. RESULTS: With no reference information, the SEM(inter) using one patient data set (Patient 1) was 0.8 mm, 2.0 mm, and 2.2 mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The use of the treatment plan as a reference reduced the SEM(inter) to 0.7 mm, 1.0 mm, and 1.6 mm in the RL, AP, and SI directions, respectively. In Patient 2, localization of the prostate was more difficult; the best SEM(inter) achieved with this patient was 0.8 mm, 1.9 mm, and 2.0 mm in the RL, AP, and SI directions, respectively. The SEM(intra) values with Patient 1 were also slightly better than with Patient 2. When reference data were used, the SEM(intra) value was 0.5 mm, 0.7 mm, and 0.5 mm for Patient 1 and 0.6 mm, 1.0 mm, and 0.7 mm for Patient 2 in the RL, AP, and SI directions, respectively. Despite the larger than expected interobserver variation reported here, the SEM(inter) was smaller than the typical day-to-day variation in prostate position. The contour alignment technique may still be useful to aid daily prostate localization or in a correction scheme to minimize the effect of target positional error. CONCLUSION: The interobserver uncertainties associated with aligning the gross target volume contours with daily CT images were sufficiently small that this method may be used for daily CT localization of the prostate. The use of a reference image is important to improve the consistency among different users in this technique.

Analysis of Variance↗

PubMed2004

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↗