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Biomedical subjects

Deborah A Kuban

Publications and source records attributed to Deborah A Kuban.

At least 19 recordsLinked to original sources
PubMed2006

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↗
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

Increasing external beam dose for T1-T2 prostate cancer: effect on risk groups.

PURPOSE: The aim of this study was to investigate effect of increasing dose on risk groups for clinical failure (CF: local failure or distant failure or hormone ablation or PSA>or=25 ng/ml) in patients with T1-T2 prostate cancer treated with external beam radiotherapy. METHODS AND MATERIALS: Patients (n=4,537) were partitioned into nonoverlapping dose ranges, each narrow enough that dose was not a predictor of CF, and risk groups for CF were determined using recursive partitioning analysis (RPA). The same technique was applied to the highest of these dose ranges (70-76 Gy, 1,136 patients) to compare risk groups for CF in this dose range with the conventional risk-group classification. RESULTS: Cutpoints defining low-risk groups in each dose range shifted to higher initial PSA levels and Gleason scores with increasing dose. Risk groups for CF in the dose range 70-76 Gy were not consistent with conventional risk groups. CONCLUSIONS: The conventional classification of risk groups was derived in the early PSA era, when total doses<70 Gy were common, and it is inconsistent with risk groups for patients treated to doses>70 Gy. Risk-group classifications must be continuously re-examined whenever the trend is toward increasing total dose.

Humans↗
PubMed2006

Comparison of biochemical failure definitions for permanent prostate brachytherapy.

PURPOSE: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. RESULTS: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. CONCLUSIONS: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable.

Adenocarcinoma↗
PubMed2005

PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis.

PURPOSE: To determine the significance of prostate-specific antigen (PSA) nadir (nPSA) and the time to nPSA (T(nPSA)) in predicting biochemical or clinical disease-free survival (PSA-DFS) and distant metastasis-free survival (DMFS) in patients treated with definitive external beam radiotherapy (RT) for clinical Stage T1b-T2 prostate cancer. METHODS AND MATERIALS: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses > or =60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T(nPSA) was calculated from the completion of RT to the nPSA date. RESULTS: A greater nPSA level and shorter T(nPSA) were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level < or =10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level >10 but < or =20 ng/mL, or Stage T2b or T2c, Gleason score < or =6, and PSA level < or =20 ng/mL, or Gleason score 7 and PSA level < or =20 ng/mL], and high [Gleason score 8-10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA > or =0.5 but <1.0 ng/mL, 52% and 96%; nPSA > or =1.0 but <2.0 ng/mL, 40% and 91%; and nPSA > or =2.0 ng/mL, 17% and 73%, respectively. The 8-year PSA-DFS and DMFS rate for patients with T(nPSA) <6 months was 27% and 66%; T(nPSA) > or =6 but <12 months, 31% and 85%; T(nPSA) > or =12 but <24 months, 42% and 94%; and T(nPSA) > or =24 months, 75% and 99%, respectively. A shorter T(nPSA) was associated with decreased PSA-DFS and DMFS, regardless of the nPSA. Both nPSA and T(nPSA) were significant predictors of PSA-DFS and DMFS in multivariate models incorporating clinical stage, Gleason score, initial PSA level, and RT dose. The significance of nPSA and T(nPSA) was supported by landmark analysis, as well as by analysis of nPSA and T(nPSA) as time-dependent covariates. A dose > or =70 Gy was associated with a lower nPSA level and longer T(nPSA) in all risk categories, and a greater dose was significantly associated with greater PSA-DFS and DMFS in multivariate analysis. Regression analysis confirmed that higher clinical stage, Gleason score, and initial PSA were associated with a greater nPSA level. CONCLUSION: The results of this large, multi-institutional analysis of 4833 patients have provided important evidence that nPSA and T(nPSA) after definitive external beam RT are not only predictive of a predominantly PSA endpoint (PSA-DFS), but are also predictive of distant metastasis in all clinical risk categories. Greater RT doses were associated with lower nPSA, longer T(nPSA), and improved PSA-DFS and DMFS.

Disease-Free Survival↗
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

Out-of-field photon and neutron dose equivalents from step-and-shoot intensity-modulated radiation therapy.

PURPOSE: To measure the photon and neutron out-of-treatment-field dose equivalents to various organs from different treatment strategies (conventional vs. intensity-modulated radiation therapy [IMRT]) at different treatment energies and delivered by different accelerators. METHODS AND MATERIALS: Independent measurements were made of the photon and neutron out-of-field dose equivalents resulting from one conventional and six IMRT treatments for prostate cancer. The conventional treatment used an 18-MV beam from a Clinac 2100; the IMRT treatments used 6-MV, 10-MV, 15-MV, and 18-MV beams from a Varian Clinac 2100 accelerator and 6-MV and 15-MV beams from a Siemens Primus accelerator. Photon doses were measured with thermoluminescent dosimeters in a Rando phantom, and neutron fluence was measured with gold foils. Dose equivalents to the colon, liver, stomach, lung, esophagus, thyroid, and active bone marrow were determined for each treatment approach. RESULTS: For each treatment approach, the relationship between dose equivalent per MU, distance from the treatment field, and depth in the patient was examined. Photon dose equivalents decreased approximately exponentially with distance from the treatment field. Neutron dose equivalents were independent of distance from the treatment field and decreased with increasing tissue depth. Neutrons were a significant contributor to the out-of field dose equivalent for beam energies > or =15 MV. CONCLUSIONS: Out-of-field photon and neutron dose equivalents can be estimated to any point in a patient undergoing a similar treatment approach from the distance of that point to the central axis and from the tissue depth. This information is useful in determining the dose to critical structures and in evaluating the risk of associated carcinogenesis.

Algorithms↗
PubMed2005

The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy.

PURPOSE: Out-of-field radiation doses to normal tissues may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Step-and-shoot intensity-modulated radiation therapy (IMRT), an increasingly popular treatment modality, yields higher out-of-field doses than do conventional treatments, because of an increase in required monitor units (beam-on time). METHODS: We used published risk coefficients (NRCP Report 116) and out-of-field dose equivalents to multiple organ sites to estimate a conservative maximal risk of fatal secondary malignancy associated with 6 IMRT approaches and 1 conventional external-beam approach for prostate cancer. RESULTS: Depending on treatment energy, the IMRT treatments required 3.5-4.9 times as many monitor units to deliver as did the conventional treatment. The conservative maximum risk of fatal second malignancy was 1.7% for conventional radiation, 2.1% for IMRT using 10-MV X-rays, and 5.1% for IMRT using 18-MV X-rays. Intermediate risks were associated with IMRT using 6-MV X-rays: 2.9% for treatment with the Varian accelerator and 3.7% for treatment with the Siemens accelerator, as well as using 15-MV X-rays: 3.4% (Varian) and 4.0% (Siemens). CONCLUSION: The risk of fatal secondary malignancy differed substantially between IMRT and conventional radiation therapy for prostate cancer, as well as between different IMRT approaches. Perhaps this risk should be considered when choosing the optimal treatment technique and delivery system for patients who will undergo prostate radiation.

Dose-Response Relationship, Radiation↗
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

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↗
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↗
PubMed2005

Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis.

PURPOSE: Pooled data on 4,839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions have previously provided long-term biochemical failure (BF) and clinical outcomes using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. In this report we determined the sensitivity and specificity of several BF definitions using distant failure (DF) alone or clinical failure (CF), defined as local failure (LF) and/or DF. MATERIALS AND METHODS: The pooled cohort was treated between 1986 and 1995 with external beam RT (60 Gy or greater) without pre-RT androgen suppression or planned post-RT adjuvant androgen suppression. Median followup was 6.3 years. The sensitivity and specificity of 102 definitions of BF relative to DF and LF were assessed. RESULTS: The BF definitions with higher sensitivity and specificity than the ASTRO definition for DF only and CF are reported. The sensitivity and specificity of the ASTRO definition to predict DF alone was 55% and 68%, respectively. Three definitions had higher sensitivity and specificity, namely prostate specific antigen (PSA) greater than current nadir (lowest PSA prior to current measurement) plus 3 ng/ml (sensitivity 76% and specificity 72%), dated at the call (failure date as the date when the criterion was met), PSA greater than absolute nadir plus 2 ng/ml (sensitivity 72% and specificity 70%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 69% and specificity 73%). The sensitivity and specificity of the ASTRO definition to predict CF was 60% and 72%, respectively. Three definitions had higher sensitivity and specificity, namely PSA greater than current nadir plus 3 ng/ml (sensitivity 66% and specificity 77%), dated at the call, PSA greater than absolute nadir plus 2 ng/ml (sensitivity 64% and specificity 74%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 67% and specificity 78%). CONCLUSIONS: Using what is to our knowledge the largest data set of patients with prostate cancer treated with RT alone we correlated multiple definitions of BF with the strict clinical end points of DF alone and CF (DF or local failure). Defining BF as PSA greater than absolute nadir plus 2 ng/ml, dated at the call, PSA greater than current nadir plus 3 ng/ml, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated, had higher sensitivity and specificity for DF alone or CF compared with the ASTRO definition. This information should contribute to the discussion regarding suggested modifications to the ASTRO definition of biochemical failure.

Adult↗
PubMed2005

Defining recurrence after radiation for prostate cancer.

PURPOSE: We reviewed prostate specific antigen (PSA) definitions of recurrence after external beam radiation for prostatic cancer and related them to the definitions used for other treatment modalities. MATERIALS AND METHODS: The literature on defining recurrence after external beam radiation, brachytherapy and prostatectomy for prostate cancer was reviewed through a MEDLINE search to ensure completeness and the inclusion of all pertinent information. RESULTS: Although the definition, which is the current standard for estimating recurrence after external beam radiation, has proved to be a reasonable measure, alternative options that are more sensitive and specific have now been defined. Similar statistical testing and comparison must also be done for other treatment modalities since the choice of failure definitions has not been evaluated nearly as thoroughly for these therapies. As much as possible, outcome reporting should be done according to the same method to ensure fairness when comparisons are made. However, inherent differences between treatment modalities and their effect on PSA production must also be considered. CONCLUSIONS: With the latest available information from patients with long-term followup PSA definitions of tumor recurrence after external beam radiation for prostatic cancer must again be reviewed in a consensus conference format. The application of a universal PSA definition of tumor recurrence across multiple treatment modalities should also be explored.

Biomarkers, Tumor↗