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Biomedical subjects

Andrew K Lee

Publications and source records attributed to Andrew K Lee.

At least 19 recordsLinked to original sources

Reducing metal artifacts in cone-beam CT images by preprocessing projection data.

PURPOSE: Computed tomography (CT) streak artifacts caused by metallic implants remain a challenge for the automatic processing of image data. The impact of metal artifacts in the soft-tissue region is magnified in cone-beam CT (CBCT), because the soft-tissue contrast is usually lower in CBCT images. The goal of this study was to develop an effective offline processing technique to minimize the effect. METHODS AND MATERIALS: The geometry calibration cue of the CBCT system was used to track the position of the metal object in projection views. The three-dimensional (3D) representation of the object can be established from only two user-selected viewing angles. The position of the shadowed region in other views can be tracked by projecting the 3D coordinates of the object. Automatic image segmentation was used followed by a Laplacian diffusion method to replace the pixels inside the metal object with the boundary pixels. The modified projection data were then used to reconstruct a new CBCT image. The procedure was tested in phantoms, prostate cancer patients with implanted gold markers and metal prosthesis, and a head-and-neck patient with dental amalgam in the teeth. RESULTS: Both phantom and patient studies demonstrated that the procedure was able to minimize the metal artifacts. Soft-tissue visibility was improved near or away from the metal object. The processing time was 1-2 s per projection. CONCLUSION: We have implemented an effective metal artifact-suppressing algorithm to improve the quality of CBCT images.

Algorithms↗

Surgically managed lymph node-positive prostate cancer: does delaying hormonal therapy worsen the outcome?

OBJECTIVES: To review our experience with the surgical management of lymph node-positive prostate cancer and to determine if there is a benefit to treating such patients with immediate rather than delayed hormonal therapy (HT). PATIENTS AND METHODS: A retrospective analysis from January 1982 to January 2001 identified 100 patients treated by radical retropubic prostatectomy (RP) either alone (70, 23 later received delayed HT) or combined with adjuvant (immediate) HT (30), with the overall median follow-up being 5.2 years. RESULTS: The median patient age at diagnosis was 58.7 years, with 20% having clinical T3 disease, and the median prostate specific antigen (PSA) level at presentation was 10 ng/mL. In 41% of patients the Gleason score on prostatic biopsy was > or = 8. After RP, 30 patients received immediate HT used as an adjuvant after surgery in the absence of any evidence of disease progression, whereas 23 received delayed HT the use of which was provoked secondary to biochemical failure (PSA threshold of 0.2-5.0 ng/mL) with no evidence of metastatic disease. A comparison of the clinical variables between the groups showed a higher median PSA level at diagnosis (P = 0.027) and biopsy Gleason score (P = 0.052) in the delayed HT group. The immediate and delayed HT groups had similar metastatic-free (P = 0.549), disease-specific (P = 0.843) and overall survival (P = 0.843). Overall, biochemical failure developed in half the patients and distant metastasis in 13%, with only nine patients dying from disease. CONCLUSIONS: Immediate and delayed HT provide similar treatment outcomes in patients with surgically managed lymph node-positive prostate cancer.

Adult↗

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↗

Influence of obesity on biochemical and clinical failure after external-beam radiotherapy for localized prostate cancer.

BACKGROUND: Several reports have shown that obesity is associated with increased risk of biochemical failure after radical prostatectomy. However, limited information is available regarding the impact of obesity on prostate cancer progression after radiotherapy. The current study sought to determine whether obesity was an independent predictor of biochemical failure (BF) and clinical recurrence (CF) among patients treated with external-beam radiotherapy (EBRT). METHODS: A retrospective analysis was performed on 873 patients receiving EBRT as the sole treatment for localized prostate cancer between 1988 and 2001. The Kaplan-Meier method, log-rank test, and Cox proportional hazards analyses were performed. RESULTS: Of the 873 patients, 18% were mildly obese and 5% were moderately to severely obese. Obesity was related to younger age at diagnosis (P < .001), more recent year of diagnosis (P = .03), and race (P = .03), with African-American men having the highest obesity rates. During a mean follow-up of 96 months, 295 patients experienced BF and 127 had CF. On multivariate analysis, controlling for clinical and treatment characteristics, increased body mass index (BMI) significantly predicted BF (hazards ratio [HR] = 1.04; 95% confidence interval [95% CI], 1.02-1.07) with a positive trend by BMI category (P = .001). Similar results were found when the outcome was CF; BMI remained an independent predictor of progression (HR = 1.05; 95% CI, 1.01-1.09), with a statistically significant trend by increased BMI category (P = .03). CONCLUSIONS: The current findings validate the important role of obesity, not only on BF but also on CF, and suggest a link to the biologic basis of tumor progression that can be therapeutically exploited.

Adult↗

Presalvage prostate-specific antigen (PSA) and PSA doubling time as predictors of biochemical failure of salvage cryotherapy in patients with locally recurrent prostate cancer after radiotherapy.

BACKGROUND: The value of presalvage cryotherapy serum PSA level in predicting biochemical failure in patients with local recurrence of prostate cancer (PCa) after radiotherapy was documented; however, little is known about the predictive value of prostate-specific antigen (PSA) doubling time (DT) in this patient group. The purpose of the current study was to evaluate serum PSA level and PSA DT as predictors of salvage cryotherapy outcomes in patients being treated for postradiotherapy locally recurrent PCa. METHODS: The charts of patients treated with salvage cryotherapy were retrospectively reviewed for locally recurrent PCa at the M. D. Anderson Cancer Center from January 1980 to July 2004. Patients who received neoadjuvant or adjuvant hormone therapy were excluded. We assessed pre- and postradiotherapy clinical data, pre- and postsalvage cryotherapy clinical data, and other variables. Kaplan-Meier and log rank tests were performed to assess unadjusted survival probabilities and 2-group survival comparisons, respectively. Cox proportional hazards regression models were used to assess the effect of patient characteristics in predicting overall, disease-specific, and biochemical failure-free survival. RESULTS: Forty-nine patients met the eligibility criteria. The median age of patients at diagnosis was 66 years (58-81 years) with the initial clinical stage before radiotherapy most commonly T2 (n = 25) or T3 (n = 21). The median presalvage cryotherapy serum PSA level was 5.9 ng/mL (0.4-23.1 ng/mL) and the presalvage prostatic biopsies were frequently high grade (Gleason grade > or =8 in 51% of patients). The median postsalvage cryotherapy serum PSA level was 0.1 ng/mL (0.1-9.5 ng/mL), and biochemical failure (defined as a serum PSA level > or =2 ng/mL above the postsalvage cryotherapy PSA nadir) occurred in 26 patients. In these 26 patients, there was a statistically significant difference between pre- and postsalvage cryotherapy PSA DTs (12.3 months to 5.6 months, respectively; P = .02). A presalvage cryotherapy serum PSA level >10 ng/mL (P = .002) and PSA DT < or =16 months (P = .06) were found to predict the subsequent risk of biochemical failure. CONCLUSIONS: Presalvage PSA and PSA DT can predict biochemical failure of salvage cryotherapy, although the predictive value of PSA DT only trended toward significance. The statistically significant difference in pre- and postsalvage cryotherapy PSA DTs was reflective of aggressive tumor biology.

Aged↗

Update on radiation therapy in prostate cancer.

Higher doses of radiation result in improved clinical control of prostate cancer,and the recent advances in prostate cancer radiotherapy are designed to escalate dose while minimizing toxicity. To achieve this goal, tighter treatment margins are needed, which require more accurate delineation of the prostate target and normal tissue at the time of treatment planning and before actual daily treatments. Modem radiation therapy techniques can deposit conformal dose virtually anywhere in the body; however, this precise therapy is of no value if it is not accurately hitting the target. Whether dose escalation is achieved by external beam techniques (eg, IMRT, protons) or brachytherapy, these ba-sic planning and delivery considerations are essentially the same. Future directions in prostate radiation therapy will use even higher radiation doses,alternative fractionation patterns, intraprostatic targets (eg, prostate tumor seen on MRI), and improved patient selection regarding which patients will benefit the most from these advanced techniques.

Dose-Response Relationship, Radiation↗

Radiation therapy combined with hormone therapy for prostate cancer.

Standard-dose radiation therapy has limited capacity to cure bulky and locally advanced prostate cancer. Multiple randomized trials have shown a clinical benefit to adding androgen suppression therapy to external-beam radiation therapy in several subsets of prostate cancer. These studies have made combining hormonal therapy with radiation therapy the standard of care for men with locally advanced (T3-4) and unfavorable prostate cancers (Gleason score >or=8 and/or prostate-specific antigen >20 ng/mL). The clinical impact of hormonal therapy has been seen in biochemical control, local control, distant metastases, disease-specific survival, and overall survival. If hormonal therapy is to be combined with radiation, it should be initiated before the start of radiation and continued during the radiation course rather than used only in the adjuvant setting. Typically, shorter-term hormone therapy is defined as regimens of 4 to 6 months, with longer-term hormone therapy describing durations beyond 24 months. Historically, longer-term hormone therapy was thought to have a more profound systemic effect; however, with the emerging use of hormonal therapy for less-advanced disease, the overall impact of shorter-course hormone therapy is being seen. This review will summarize trials using hormonal therapy and radiation with an emphasis on phase III studies and describe the more recent integration of hormone therapy with radiation for prostate cancer.

Androgen Antagonists↗

Utility of prostate-specific antigen kinetics in addition to clinical factors in the selection of patients for salvage local therapy.

A detectable and rising prostate-specific antigen (PSA) level after radical prostatectomy or a rising PSA above the nadir value after radiation therapy may represent a local failure, distant failure, or both. Determining the site or sites of failure is critical for selecting the appropriate salvage therapy. Nevertheless, although PSA failure precedes clinically evident failure by several years, determining the source of the biochemical failure is often not possible using currently available diagnostic studies. Selecting the optimal therapeutic approach may be guided by the initial clinical factors (eg, T-category, PSA, biopsy Gleason score). If the patient has had a radical prostatectomy, then the pathologic outcomes of the surgery (eg, pathologic T-category and prostatectomy Gleason score, nodal and margin status) may provide further information. Beyond pretreatment clinical and post-treatment pathologic factors, PSA kinetics, and specifically a pretreatment PSA velocity > 2 ng/mL/year, an interval to PSA failure < 3 years and a post-treatment PSA doubling time < 3 months place a man at increased risk for metastases and subsequent prostate cancer-specific mortality, making these men poor candidates for local-only salvage therapy. Therefore, the optimal candidate for local-only salvage therapy is a man whose pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal vesicle or lymph node involvement.

Biomarkers, Tumor↗

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↗

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↗

Symptomatic local recurrence of prostate carcinoma after radiation therapy.

BACKGROUND: Symptomatic local recurrence of prostate carcinoma (SLRPC) after radiation therapy (RT) is associated with morbidity and debilitating symptoms that have a substantial impact on the patient's quality of life. Most reports on the results of RT for localized prostate carcinoma (PC) do not address this endpoint. The objective of this study was to determine the incidence of SLRPC and to identify the risk factors for this endpoint. METHODS: The medical charts of 1006 patients who received RT for localized PC at the University of Texas M. D. Anderson Cancer Center between 1987 and 1997 were reviewed. Local symptoms were defined as hematuria, voiding symptoms, urinary obstruction, and pelvic pain. Progressive symptoms accompanied by either confirmatory histology or cystoscopic findings were attributed to PC. Univariate and multivariate analyses using Cox proportional hazards models were applied to identify risk predictors. RESULTS: Among 964 patients for whom follow-up data were available, 277 patients had prostate-specific antigen (PSA) progression, and 45 patients died of PC during a median follow-up of 9.4 years. In total, 33 patients (3.4%) developed SLRPC. In patients who experienced biochemical progression, the actuarial 5-year incidence of SLRPC was 8.3%. Among the patients who had developed SLRPC, 23 patients (69.7%) died of PC at a median of 25.3 months from the onset of local symptoms. Adverse histologic tumor subtypes (ductal, small cell, and sarcomatoid) were associated significantly with SLRPC (hazard ratio, 8.4; 95% confidence interval, 2.99-23.63). Clinical T classification at diagnosis, Gleason score, and initial PSA level showed a trend toward an increased hazard ratio. CONCLUSIONS: SLRPC after radiotherapy therapy was an uncommon but clinically significant event. Aggressive histologic subtypes were predictive of this endpoint. Clinical T classification, Gleason score, and initial prostate-specific antigen levels also may have predictive value.

Aged↗

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↗

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↗

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↗

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↗

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↗

Mortality after cure of testicular seminoma.

PURPOSE: To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). PATIENTS AND METHODS: From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with post-orchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. RESULTS: After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P <.01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P <.01). An increased mortality was evident in patients treated with and without mediastinal XRT. CONCLUSION: Long-term survivors of seminoma treated with post-orchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.

Actuarial Analysis↗

Rise in serum PSA of 1.5 ng/mL above 24-month nadir after external beam radiotherapy is predictive of biochemical failure.

OBJECTIVES: To determine whether a rise in the serum prostate-specific antigen (PSA) concentration 24 months or later after completion of external beam radiotherapy (EBRT) for prostate cancer could predict for biochemical failure. METHODS: We evaluated the records of 1006 patients who had undergone full-dose EBRT alone as primary treatment for T1-T4NxM0 prostate cancer at our institution between April 1987 and January 1998. Patients who had biochemical failure--as determined by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition--prior to 24 months after EBRT were excluded. PSA increases of four different magnitudes (0.5, 0.8, 1.0, and 1.5 ng/mL above the 24-month nadir) were evaluated for their ability to predict ASTRO-defined biochemical failure. RESULTS: A total of 745 patients met the analysis criteria. The rate of ASTRO-defined biochemical failure in patients with a PSA increase of 0.5, 0.8, 1.0, and 1.5 ng/mL above the 24-month nadir was 56%, 64%, 66%, and 71%, respectively. An increase of 1.5 ng/mL or more had a sensitivity of 80% and a specificity of 88% in the prediction of biochemical failure, with an accuracy of 86%. CONCLUSIONS: A PSA increase of 1.5 ng/mL or more above the 24-month nadir can be used to predict for ASTRO-defined failure after EBRT and may be used to identify patients at risk early-on.

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