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Purpose: The purpose of this study was to evaluate and compare the Complete Ophthalmic Analysis System (COAS) G200 Aberrometer (Wavefront Sciences Inc., Albuquerque, NM) and Canon RK-F1 Autorefractor (Canon Inc., Tokyo, Japan) for measuring refractive errors in young children., Methods: The Sydney Myopia Study is a population-based study of refractive error and eye health in young Australian children. Cycloplegic refractions were performed on 1504 school year 1 students (mostly 6 years old) and 890 school year 7 (mostly 12 years old) students using both the COAS G200 Aberrometer and Canon RK-F1 autorefractor. Refractive data were analyzed using power vectors. Mean differences and 95% limits of agreement were determined for refractive components between the two instruments., Results: The mean age +/- standard deviation was 6.7 +/- 0.4 years (range, 5.5-9.1 years) and 12.6 +/- 0.5 years (range, 11.1-14.4 years) for the year 1 and year 7 students, respectively. Mean paired differences for the M component (spherical equivalent) between the COAS G200 and Canon RK-F1 were <0.25 D in both age groups and were statistically significant in the year 1 group only (p < 0.001). Small significant differences were found in the astigmatic components (J0 and J45) in both groups. A smaller coefficient of agreement for the M component was found in the older group (0.54 D), whereas the coefficients of agreement of the astigmatic components (J0 and J45) were similar for both groups., Conclusions: The COAS G200 aberrometer was an easy-to-use instrument for the measurement of refractive error in children. In addition to being able to measure higher and lower order aberrations, the COAS G200 provides refractive error measurements comparable to those of an autorefractor.

Background: The posttreatment prostate-specific antigen (PSA) bounce phenomenon has been recognized in at least 20% of all patients treated with radiation. The purpose of the current report was to determine if there was a difference in biochemical and clinical control between the bounce and nonbounce (NB) patients using pooled data on 4839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions between 1986 and 1995., Methods: The median follow-up was 6.3 years. A posttreatment PSA bounce was defined by a minimal rise of 0.4 ng/mL over a 6-month follow-up period, followed by a drop in PSA level of any magnitude. Endpoints included no biochemical evidence of disease (bNED) failure (BF) (ASTRO definition), distant failure (DF), cause-specific failure (CSF), and overall survival (OS). Patients were stratified by pretreatment PSA, Gleason score, T stage, age, dose, and risk group., Results: In all, 978 (20%) patients experienced at least 1 posttreatment PSA bounce. Within 3 subgroups (risk group, pretreatment PSA, and age), statistically significant differences of remaining bounce-free were observed on univariate analysis. Patients < 70 years had a 72% chance of remaining bounce-free at 5 years compared with 75% for older patients (P = .04). The NB patients had 72% bNED control at 10 years compared with 58% for the bounce patients. The effect of a bounce remained statistically significant on multivariate analysis (P < .0001). No statistically significant difference in DF, CSF, or OS was observed., Conclusions: Patients treated with external beam radiation therapy alone who experience a posttreatment PSA bounce have increased risk of BF. However, this did not translate into a difference in clinical failure with the available follow-up in the current study., ((c) 2006 American Cancer Society.)

Purpose: Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Age has been associated with worse outcome in univariate analysis. However, the patterns of failure and associated risk factors in older patients remain unclear. We reviewed our institution's experience to assess the effect of age in a population of endometrial cancer patients treated with surgery and adjuvant radiation therapy., Methods: From 1992-2002, 243 endometrial cancer patients underwent a total abdominal hysterectomy and adjuvant radiation. Forty-nine patients with stage I-II (occult) endometrial adenocarcinoma (no clear cell or serous papillary) were treated postoperatively with vaginal intracavitary high-dose rate (HDR) brachytherapy alone using Iridium-192 (median dose 30 Gy) to a median length of 4 cm. Forty-eight patients with stage I-III endometrial adenocarcinoma (no clear cell or papillary serous) were treated with postoperative pelvic RT (median dose 45 Gy) and intracavitary HDR brachytherapy (median dose 20 Gy). One hundred forty-six patients underwent postoperative whole abdomino-pelvic irradiation (WAPI) secondary to unfavorable histology (clear cell or serous papillary) or two of the following: deep myometrial invasion, grade 3, or FIGO stage III. Age was analyzed as a continuous and a categorical variable. The age of 63 year split the age group using various statistical analyses., Results: Median follow-up of all patients was 4.2 years. Patients grouped by age of < or =63 years or older had similar FIGO stage (P = 0.5), grade (P = 0.09), treatment modality (P = 0.7), and lymphovascular space invasion (LVSI) (P = 0.6). Twenty-five percent (60/243) of patients developed recurrence. Of these failures, 15% (15/102) were age < or =63 years and 32% (45/141) were age >63 years at diagnosis (P = 0.02). For all patients, the 5-year event-free survival (EFS), cause specific survival (CSS), and overall survival (OS) were 64%, 82%, and 72%, respectively. Five-year EFS for patients age < or =63 years and >63 years was 76% vs. 55% (P < 0.001). Five-year OS for age < or =63 years and >63 years was 85% vs. 63% (P < 0.001). Five-year CSS for age < or =63 years and >63 years was 91% vs. 75% (P = 0.003). Various factors were analyzed to determine an association with age. Older patients with stage III-IVA had significantly more failures than patients less than age 63 (P = 0.002). Older patients (>63 years) were found to have serous papillary histology (28%) more often than younger patients (15%) (P = 0.02). Greater depth of invasion was associated with older age (P = 0.01). On univariate analysis, older age (P = 0.003), LVSI (P = 0.002), FIGO stage (P < 0.001), grade (P < 0.001), and depth of invasion (P = 0.03) predicted for failure. On Cox multivariate analysis, older age (P = 0.006, HR 2.83), higher FIGO stage (P = 0.001, HR 1.96), and higher grade (P = 0.002, HR 2.66) were significant prognostic factors for recurrence. No difference was seen between the two age groups from date of surgery and start of radiation. The duration of therapy was not different between the two groups., Conclusions: Older endometrial cancer (age >63 years) patients have a significantly decreased overall survival, cause-specific survival, and greater risk of recurrence following postoperative RT independent of other prognostic factors and/or treatment technique. The impact of treatment-related variables did not alter the age-related outcome.

Objective: Adding pelvic radiation to high-dose prostate radiation for prostate cancer patients with a >15% risk of positive lymph nodes (LN) is controversial. We performed a matched-pair analysis of patients treated at 2 institutions to assess the impact of pelvic radiotherapy (P-RT)., Methods: From January 1993 to March 2003, 2 institutions treated 1432 prostate cancer patients with combined external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy. Those receiving EBRT were treated either to the prostate and seminal vesicles alone or to the entire pelvis (46 Gy). In all cases, prostate dose (EBRT and HDR) resulted in an average BED >100 Gy (alpha/beta = 1.2). There were 755 cases identified as having a pelvic LN risk >15% using the Roach formula. Of these, 255 cases were treated without pelvic RT and randomly matched by Gleason score, T stage, and pretreatment PSA to 500 cases treated with pelvic RT, resulting in 250 pairs (1:1)., Results: Median follow-up was 4.0 years (P = 0.7). The 4-year prostate biochemical failure (22% versus 14%, P = 0.12), distant metastasis (9% versus 4%, P = 0.6), event-free survival (72% versus 78%, P = 0.3), prostate cancer death rate (4% versus 2%, P = 0.9), and overall survival (89% versus 88%, P = 0.7) were not significantly different for patients treated with and without P-RT. Analysis with and without androgen deprivation therapy showed similar results., Conclusion: Improved biochemical, clinical, or survival outcomes were not observed for prostate cancer patients at risk for positive pelvic LN >15% when treated with high-dose EBRT and HDR brachytherapy to the prostate with or without pelvic radiation.

A case of fracture of the ceramic head of a total hip arthroplasty is presented, which was a total cementless arthroplasty with ceramic-on-ceramic articulation. No history of trauma was observed. The arthroplasty was revised, and a new cementless arthroplasty with a polyethylene insert and a metal head was inserted. The result has been satisfactory.

Objective: To evaluate outcomes of intermediate- and high-risk prostate cancer patients on a prospective dose-escalation study of pelvic external-beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost., Methods: From November 1991 to April 2003, 197 patients were treated for intermediate- and high-risk disease features. All patients had prostate-specific antigen>10 ng/ml, Gleason score>or=7, or clinical stage>or=T2b, and all received pelvic EBRT (46 Gy) while receiving either two or three HDR boost treatments. HDR dose fractionation increased progressively and was divided into two dose levels. The mean prostate biologic equivalency dose was 88.2 Gy for the low-dose group and 116.8 Gy for the high-dose group (alpha/beta=1.2). Clinical failure was either local failure or distant metastasis; clinical event-free survival (cEFS) was defined as patients who lived free of clinical failure., Results: Median follow-up was 4.9 years. The 5-year rates were as follows: biologic failure (BF), 18.6%, clinical failure (CF), 9.8%, cEFS 84.8%, cause-specific survival (CSS), 98.3%, and overall survival (OS), 92.9%. Five-year biochemical failure (68.7% vs. 86%, p<0.001), CF (6.1% vs. 15.6%, p=0.04), cEFS (75.5% vs. 91.7%, p=0.003), CSS (95.4% vs. 100%, p=0.02), and OS (86.2% vs. 97.8%, p=0.002) were significantly better for the high-dose group. Multivariate analysis showed that high-dose group (p=0.01, HR 0.35) and Gleason score (p=0.01, HR 1.84) were significant variables for cEFS. Multivariate analysis showed that high-dose group (p=0.01, HR 0.14) and age (p=0.03, HR 1.09 per year) were significant variables for overall survival., Conclusion: There is a strong dose-response relationship for intermediate- to high-risk prostate cancer patients. Improved locoregional control with higher radiation doses alone can significantly decrease biochemical and clinical failures.

Purpose: We performed a complete pathologic analysis examining extracapsular extension (ECE) and microscopic spread of malignant cells beyond the prostate capsule to determine whether and when clinical target volume (CTV) expansion should be performed., Methods and Materials: A detailed pathologic analysis was performed for 371 prostatectomy specimens. All slides from each case were reviewed by a single pathologist (N.S.G.). The ECE status and ECE distance, defined as the maximal linear radial distance of malignant cells beyond the capsule, were recorded., Results: A total of 121 patients (33%) were found to have ECE (68 unilateral, 53 bilateral). Median ECE distance=2.4 mm [range: 0.05-7.0 mm]. The 90th-percentile distance = 5.0 mm. Of the 121 cases with ECE, 55% had ECE distance>or=2 mm, 19%>or=4 mm, and 6%>or=6 mm. ECE occurred primarily posterolaterally along the neurovascular bundle in all cases. Pretreatment prostrate-specific antigen (PSA), biopsy Gleason, pathologic Gleason, clinical stage, bilateral involvement, positive margins, percentage of gland involved, and maximal tumor dimension were associated with presence of ECE. Both PSA and Gleason score were associated with ECE distance. In all 371 patients, for those with either pretreatment PSA>or=10 or biopsy Gleason score>or=7, 21% had ECE>or=2 mm and 5%>or=4 mm beyond the capsule. For patients with both of these risk factors, 49% had ECE>or=2 mm and 21%>or=4 mm., Conclusions: For prostate cancer with ECE, the median linear distance of ECE was 2.4 mm and occurred primarily posterolaterally. Although only 5% of patients demonstrate ECE>4 to 5 mm beyond the capsule, this risk may exceed 20% in patients with PSA>or=10 ng/ml and biopsy Gleason score>or=7. As imaging techniques improve for prostate capsule delineation and as radiotherapy delivery techniques increase in accuracy, a posterolateral CTV expansion should be considered for patients at high risk.

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.

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.

Background: The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using interstitial brachytherapy., Methods: From April 1993 to December 2001, 199 patients with Stage I-II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at < or = 6 months, 2 years, and 5 years., Results: The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95-99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years., Conclusions: APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95-99% of patients and stabilized at 2 years.

Purpose: To evaluate the result of the surgical correction of esotropic patients with eccentric fixation and to compare it with operated on esotropic patients who did not have this sensorial disorder., Methods: A retrospective study of the result of the surgical correction of essential esotropia in 19 patients with eccentric fixation of the "Santa Casa de São Paulo". As group controls, 17 esotropic patients with strabismic amblyopia and central fixation and 16 esotropic patients without amblyopia who had been operated on. The statistical test was application of variance for proportions (ANOVA)., Results: In the 3 studied groups undercorrection prevailed, 12 (63.2%) cases in group I, 13 (76.5%) cases in group II and 13 (81.3%) patients in group III. The surgical success occurred in 7 (36.8%) patients of the group with eccentric fixation, of whom 4 cases were overcorrected and 3 of orthotropia. In group II, of the 7 cases of surgical success, 3 (17.6%) had orthotropia and 1 (5.9%) case presented with overcorrection. In group III, we had 5 (31.3%) cases of surgical success, 1 (6.3%) of them with orthotropia. Among the 36 amblyopic patients, 5 (13.9%) presented overcorrection. The standard error of the average of the surgical correction was 4.6 in the group of patients with eccentric setting. ANOVA test for the average of the surgical correction was p=0.349. Considering the good result (a deviation smaller than 10delta), the statistical analysis revealed a p=0.847., Conclusion: The eccentric setting did not represent a determinant factor in the surgical result (good versus bad) of the horizontal surgical alignment.

Purpose: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started., Methods and Materials: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage < or = T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years., Results: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No significant difference by dose level was seen in the 2-year rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%, 14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and 79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035)., Conclusions: High doses (79.2 Gy) were safely delivered in selected patients by our adaptive radiotherapy process. Under the rectal dose-volume histogram constraints for the dose level selection, the risk of chronic rectal toxicity is similar among patients treated to different dose levels. Therefore, rectal chronic toxicity rates reflect the dose-volume cutoff used and are independent of the actual dose levels. On the other hand, a larger PTV will increase the rectal wall dose and chronic rectal toxicity rates. PTV volume and dose constraints should be defined, considering their potential benefit.

Purpose: High-dose radiotherapy, delivered in an accelerated hypofractionated course, was utilized to treat prostate cancer. Therapy consisted of external beam radiotherapy (EBRT) and transrectal ultrasound (TRUS)-guided conformally modulated high-dose rate (HDR) brachytherapy. The purpose of this report is (1) to assess long-term comparative outcomes from three trials using similar accelerated hypofractionated regimes; and (2) to examine the long-term survival impact of a short course of < or =6 months adjuvant/concurrent androgen deprivation when a very high radiation dose was delivered., Methods and Materials: Between 1986 and 2000, 1,260 patients were treated at three institutions with pelvic EBRT (36-50 Gy) integrated with HDR prostate brachytherapy. The total dose including brachytherapy was given over 5 weeks. The biologic equivalent EBRT dose ranged between 90 and 123 Gy (median, 102 Gy) using an alpha /beta of 1.2. Patient eligibility criteria included a pretreatment prostate-specific antigen > or =10, Gleason score > or =7, or clinical stage > or =T2b. A total of 1,260 patients were treated, and 934 meet the criteria. Kiel University Hospital treated 198 patients; William Beaumont Hospital, 315; and California Endocurietherapy Cancer Center, 459 patients. Brachytherapy dose regimes were somewhat different between centers and the dose was escalated from 5.5 x 3 to 15 Gy x 2 Gy. Patients were divided for analysis between the 406 who received up to 6 months of androgen deprivation therapy and the 528 patients who did not. All patients had a minimum follow-up of 18 months (3 times the exposure to androgen deprivation therapy). The American Society for Therapeutic Radiology and Oncology biochemical failure definition was used., Results: Mean age was 69 years. Median follow-up time was 4.4 years (range, 1.5-14.5); 4 years for androgen deprivation therapy patients and 4.9 for radiation alone. There was no difference at 5 and 8 years in overall survival, cause-specific survival, or biochemical control among the three institutions. The corresponding 8-year rates with and without androgen deprivation therapy were biochemical control 85% and 81%; overall survival 83% and 78%; cause-specific survival 89% and 94%; and metastatic rates of 16.6% and 7.3%. A multivariate analysis revealed androgen deprivation therapy did not predict for biochemical failure for either the entire group or the subset of 177 patients harboring all three poor prognostic factors. Moreover, adding androgen deprivation therapy strongly correlated with higher rates of both metastasis (p = 0.09; hazard ratio, 2.08) and cancer-related deaths (p = 0.02, hazard ratio 3.25). These negative results for the most unfavorable group led us to question if androgen deprivation therapy might have a deleterious impact through delay in delivery of the potentially curative radiation or whether there may be a biologic basis by fixing the cycling cells in G0., Conclusions: Accelerated hypofractionated pelvic EBRT integrated with TRUS-guided conformally modulated HDR administered to 1,260 patients in three institutions was an excellent method of delivering very high radiation dose to the prostate in 5 weeks. Similar high overall, cause-specific, and biochemical no evidence of disease survival rates achieved show that prostate HDR can be successfully delivered in academic and community settings. At 8 years, the addition of a course of < or =6 months of neoadjuvant/concurrent androgen deprivation therapy to a very high radiation dose did not confer a therapeutic advantage but added side effects and cost. Furthermore, for the most unfavorable group, there was a higher rate of distant metastasis and more prostate cancer-related deaths. We question the value of a short course of androgen deprivation therapy when used with high-dose radiation.

Purpose: Kilovoltage cone-beam CT (CBCT) implemented on board a medical accelerator is available for image-guidance applications in our clinic. The objective of this work was to assess the magnitude and stability of the residual setup error associated with CBCT online-guided prostate cancer patient setup. Residual error pertains to the uncertainty in image registration, the limited mechanical accuracy, and the intrafraction motion during imaging and treatment., Methods and Materials: The residual error for CBCT online-guided correction was first determined in a phantom study. After online correction, the phantom residual error was determined by comparing megavoltage portal images acquired every 90 degrees to the corresponding digitally reconstructed radiographs. In the clinical study, 8 prostate cancer patients were implanted with three radiopaque markers made of high-winding coils. After positioning the patient using the skin marks, a CBCT scan was acquired and the setup error determined by fusing the coils on the CBCT and planning CT scans. The patient setup was then corrected by moving the couch accordingly. A second CBCT scan was acquired immediately after the correction to evaluate the residual target setup error. Intrafraction motion was evaluated by tracking the coils and the bony landmarks on kilovoltage radiographs acquired every 30 s between the two CBCT scans. Corrections based on soft-tissue registration were evaluated offline by aligning the prostate contours defined on both planning CT and CBCT images., Results: For ideal rigid phantoms, CBCT image-guided treatment can usually achieve setup accuracy of 1 mm or better. For the patients, after CBCT correction, the target setup error was reduced in almost all cases and was generally within +/-1.5 mm. The image guidance process took 23-35 min, dictated by the computer speed and network configuration. The contribution of the intrafraction motion to the residual setup error was small, with a standard deviation of +/-0.9 mm. The average difference between the setup corrections obtained with coil and soft-tissue registration was greatest in the superoinferior direction and was equal to -1.1 +/- 2.9 mm., Conclusion: On the basis of the residual setup error measurements, the margin required after online CBCT correction for the patients enrolled in this study would be approximatively 3 mm and is considered to be a lower limit owing to the small intrafraction motion observed. The discrepancy between setup corrections derived from registration using coils or soft tissue can be due in part to the lack of complete three-dimensional information with the coils or to the difficulty in prostate delineation and requires further study.

Purpose: To quantify prostate motion during a radiation therapy treatment using cine-magnetic resonance imaging (cine-MRI) for time frames comparable to that expected in an image-guided radiation therapy treatment session (20-30 min)., Materials and Methods: Six patients undergoing radiation therapy for prostate cancer were imaged on 3 days, over the course of therapy (Weeks 1, 3, and 5). Four hundred images were acquired during the 1-h MRI session in 3 sagittal planes through the prostate at 6-s intervals. Eleven anatomic points of interest (POIs) have been used to characterize prostate/bony pelvis/abdominal wall displacement. Motion traces and standard deviation for each of the 11 POIs have been determined. The probability of displacement over time has also been calculated., Results: Patients were divided into 2 groups according to rectal filling status: full vs. empty rectum. The displacement of POIs (standard deviation) ranged from 0.98 to 1.72 mm for the full-rectum group and from 0.68 to 1.04 mm for the empty-rectum group. The low standard deviations in position (2 mm or less) would suggest that these excursions have a low frequency of occurrence. The most sensitive prostate POI to rectal wall motion was the mid-posterior with a standard deviation of 1.72 mm in the full-rectum group vs. 0.79 mm in the empty-rectum group (p = 0.0001). This POI has a 10% probability of moving more than 3 mm in a time frame of approximately 1 min if the rectum is full vs. approximately 20 min if the rectum is empty., Conclusion: Motion of the prostate and seminal vesicles during a time frame similar to a standard treatment session is reduced compared to that reported in interfraction studies. The most significant predictor for intrafraction prostate motion is the status of rectal filling. A prostate displacement of <3 mm (90%) can be expected for the 20 min after the moment of initial imaging for patients with an empty rectum. This is not the case for patients presenting with full rectum. The determination of appropriate intrafraction margins in radiation therapy to accommodate the time-dependent uncertainty in positional targeting is a topic of ongoing investigations for the on-line image guidance model.

Background and Purpose: X-ray volumetric imaging system (XVI) mounted on a linear accelerator is available for image guidance applications. In preparation for clinical implementation, phantom and patient imaging studies were conducted to determine the irradiation parameters that would trade-off image quality, patient dose and scanning time., Patients and Methods: The XVI image quality and imaging dose were benchmarked against those obtained with a helical CT scanner for a head and body phantom. The irradiation parameters were varied including the total imaging dose, number of projections, field of view, reconstruction resolution and use of a scatter rejection grid. We characterized the image quality based on relative contrast, noise, contrast to noise ratio (CNR) and point spread function (PSF). XVI scans of pelvis, head and neck and lung patients were acquired and submitted to a range of observers to identify the favorable reconstruction parameters., Results: Phantom studies have demonstrated that a scatter rejection grid reduces photon scattering and improves the image uniformity. For the body phantom, the helical CT and the wide field XVI technique produce similar image quality, with surface doses of 0.025 and 0.044 Gy respectively. We have demonstrated that the local tomography technique improves the image contrast and the CNR while reducing the skin dose by 40-50% compared to the wide field technique. Clinical scans of head and neck, lung and prostate patients present good soft tissue contrast and excellent bone definition., Conclusions: With adjustment of irradiation parameters and an imaging surface dose of less than 0.05 Gy, high quality XVI images can be obtained for a phantom simulating the body thickness. XVI is currently feasible for image-guided treatments of head and neck, torso and pelvic areas using soft tissue and bony structures.

Objective: Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99., Methods: From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I-II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively., Results: Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% (n = 2), 2% (n = 3), and 9% (n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs. 34% (P value < 0.001), and GI obstruction 0% vs. 7% (P value = 0.08)., Conclusion: Stage I-II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.

Purpose: Heart dose-volume analysis using computed tomography (CT) is limited because of motion artifact and poor delineation between myocardium and ventricular space. We used dedicated cardiac magnetic resonance imaging (MRI) to quantify exclusion of left ventricular (LV) myocardium via active breathing control (ABC) during left breast irradiation and to determine the correlation between irradiated whole heart and LV volumes., Methods and Materials: Fifteen patients who completed adjuvant irradiation for early-stage left breast cancer participated. Treatment consisted of 45 Gy to the entire breast using ABC followed by a 16-Gy electron boost to the lumpectomy cavity. Patients underwent planning CT scans in free breathing (FB) and moderate deep inspiration breath hold (mDIBH). Electrocardiogram-gated cardiac MRI was performed in the treatment position using alpha-cradle immobilization. MRI scans were acquired in late diastole (LD), mid-diastole (MD), and systole (S) for both FB and mDIBH. After image fusion with the patients' radiation therapy planning CT scan, MRI LV volumes were defined for the three examined phases of the cardiac cycle, and comparative dose-volume analysis was performed., Results: Cardiac volume definition was found to differ significantly because of combinations of respiratory and intrinsic heart motion. The fraction of LV myocardium receiving 50% (22.5 Gy) of the prescribed whole breast dose (V(22.5)) was reduced by 85.3%, 91.8%, and 94.6% via ABC for LD, MD, and S, respectively. Linear regression revealed strong correlation between MRI-defined whole heart and LV V(22.5) reduction via ABC, suggesting that LV myocardium accounts for up to approximately 50% of the excluded heart volume through this technique. Significant but weaker correlations were noted between CT-defined whole heart and LV V(22.5) reductions with marked variability in the measurements of patients with larger amounts of heart in the treatment field., Conclusions: Cardiac MRI demonstrated a significant reduction in LV myocardium irradiated with the use of ABC. The correlation between reduction in V(22.5) values for LV wall and CT-defined whole heart suggests that CT is adequate for determining which patients are likely to benefit from ABC treatment, but inaccuracies inherent to standard CT dictate that more detailed imaging studies such as MRI are required for accurate cardiotoxicity assessment.

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.

Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT., Methods and Materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level > or =0.1 ng/mL and any postoperative PSA level > or =0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT., Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA <0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the 5-year BC rate was 52% for RP+RT vs. 30% for RP (p < 0.01). The 5-year BC rate for patients with seminal vesicle invasion was 60% for RP+RT vs. 18% for RP (p < 0.01). For those with positive margins, the 5-year BC rate was 64% for RP+RT vs. 27% for RP (p < 0.01). The use of adjuvant RT remained statistically significant on multivariate analysis when applying either biochemical failure definition. Adjuvant RT also remained statistically significant when including the postoperative PSA level (>30 days after surgery) in the multivariate analyses. In addition, 99 (17%) of the 583 RP patients required salvage prostatic fossa RT (median dose, 59.4 Gy) at a median interval of 1.3 years after surgery (range, 0.1-8.4) for a palpable recurrence (n = 10) or a detectable/rising postoperative PSA level (n = 89). The median PSA level before salvage RT was 0.8 ng/mL (mean, 3.2 ng/mL). The 5-year and 8-year BC rate, using the PSA <0.1 ng/mL definition, from the date of salvage RT was 41% and 35%, respectively. The 5-year and 8-year BC rate, using the PSA <0.3 ng/mL definition, was 46% and 36%, respectively. The 8-year local recurrence rate after salvage RT was 4%., Conclusion: Adjuvant RT demonstrated improved efficacy against prostate cancer. For patients with poor pathologic features (extracapsular extension, seminal vesicle invasion, positive margins), adjuvant RT improved the biochemical outcome independent of other prognostic factors.

Purpose: We report the first single-institutional dosimetric comparison of patients treated with three forms of accelerated partial breast irradiation: interstitial HDR brachytherapy, the MammoSite balloon apparatus, and 3D conformal external beam quadrant irradiation (3D-CRT)., Methods: A retrospective dosimetric comparison of interstitial HDR brachytherapy, MammoSite balloon brachytherapy, and 3D-CRT was performed. Thirty patients including 10 from each treatment technique were included for a dosimetric comparison of the dose received by the ipsilateral breast, PTV, heart, and ipsilateral lung. Interstitial patients were treated with 4 Gy in 8 fractions to 32 Gy, and the MammoSite patients were treated with 3.4 Gy in 10 fractions to 34 Gy. 3D-CRT patients were treated with 3.85 Gy in 10 fractions to 38.5 Gy using multiple isocentric beams. The CT images from simulation or implant evaluation were transferred into our 3D treatment planning software. The lumpectomy cavities were outlined for every patient, except the MammoSite patients, where the cavity was defined by the balloon edge. The PTV was constructed as a uniform expansion of 1.5 cm for all interstitial HDR patients, 1.0 cm for the MammoSite patients, and a 1.0 cm expansion in addition to the CTV expansion of 1.0 cm (n=2), and 1.5 cm (n=8) for the 3D-CRT patients. The CTV expansion for 3D-CRT and the PTV expansion for the brachytherapy patients were limited to the chest wall and skin. Normal structures including both ipsilateral lung and breast and heart for left-sided lesions were outlined. The lumpectomy cavity was subtracted from the PTV and normal breast tissue for evaluation. To evaluate dose to the ipsilateral breast and lung, PTV, and heart, a dose-volume histogram (DVH) analysis was performed. All histograms were normalized to the volume of the structure (i.e., expressed as percent volume)., Results: The average percentage of the breast receiving 100% and 50% of the prescribed dose (PD) was higher in the 3D-CRT group (24% and 48%, respectively) compared with the MammoSite (5% and 18%, respectively) and interstitial patients (10% and 26%, respectively). Improved coverage of the PTV was noted in the 3D-CRT plans compared with the MammoSite and interstitial HDR plans. With the interstitial HDR technique, 58% of the PTV received 100% of the PD compared with 76% with MammoSite and 100% with 3D-CRT techniques. The percentage of the PTV receiving 90% of the PD was 68%, 91%, and 100% for the interstitial HDR, MammoSite, and 3D-CRT patients, respectively. The ipsilateral lung V20 was slightly higher for 3D-CRT at 5% compared with 0% for both brachytherapy techniques., Conclusion: In those treated with 3D-CRT, coverage of the PTV was better with 3D-CRT but varied with the definition used. At the coverage at 90% of the PD, no difference was observed between 3D-CRT and MammoSite (which were both better than interstitial). 3D-CRT resulted in better coverage of the PTV compared with MammoSite or interstitial brachytherapy techniques. Better PTV coverage with 3D-CRT came at the cost of a higher integral dose to the remaining normal breast. Dosimetrically, the best partial breast irradiation technique appears to depend on the clinical situation. Of the brachytherapy techniques, MammoSite appears to be superior in PTV coverage. When comparing MammoSite vs. 3D-CRT PTV coverage at 90% of the PD, the difference was not significantly different.

Purpose: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is now considered the most accurate clinical staging study for non-small-cell lung cancer (NSCLC) and is also important in the staging of multiple other malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is typically based entirely on computed tomographic data. We performed a series of phantom studies to determine an accurate and uniformly applicable method for defining a GTV with FDG-PET., Methods and Materials: A model-based method was tested by a phantom study to determine a threshold, or unique cutoff of standardized uptake value based on body weight (standardized uptake value [SUV]) for FDG-PET based GTV definition. The degree to which mean target SUV, background FDG concentration, and target volume influenced that GTV definition were evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank. Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within the tank, with a minimum separation of 4 cm between the edges of the spheres. The sphere volumes were selected based on the range of NSCLC patient tumor volumes seen in our clinic. The tank and spheres were filled with a variety of known concentrations of FDG in several experiments and then scanned using a General Electric Advance PET scanner. In the initial experiment, six spheres with identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85 approximately 9.68) and suspended within a background bath of FDG at a similar concentration to that used in clinical practice (0.144 muCi/mL). The second experiment was identical to the first, but was performed at 0.144 and 0.036 muCi/mL background concentrations to determine the effect of background FDG concentration on sphere definition. In the third experiment, six spheres with volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and suspended in a standard background FDG concentration of 0.144 muCi/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators., Results: There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 x (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms., Conclusions: An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process.

Purpose: The purpose of this analysis was to evaluate patterns and rates of ipsilateral breast tumor recurrence (IBTR) over time based on the type of failure (true recurrence/marginal miss [TR/MM] vs. elsewhere [E]) and to compare these to rates of contralateral failure in women with Stages I/II breast cancer treated with conservative surgery (CS) and radiation therapy (RT)., Methods and Materials: Between 1980 and 1997, 1448 patients with Stages I/II invasive breast carcinoma were treated with CS and RT to a median total dose of >60 Gy. IBTRs were analyzed in terms of their location as follows: TR/MM, referring to those occurring in the same quadrant, and E, referring to the development of a malignancy remote from the index lesion. Outcomes were characterized in terms of their temporal recurrence patterns and correlated with rates of contralateral breast failure (CL). The median follow-up was 8.5 years., Results: A total of 79 ipsilateral and 98 contralateral failures were observed during the follow-up period corresponding to 5-, 10-, and 15-year actuarial rates of 2%, 7%, and 10% and 4%, 9%, and 12% respectively. Fifty-nine ipsilateral failures (74.7%) were designated as TR/MM and 20 (25.3%) as E. The corresponding 5-, 10-, and 15-year actuarial rates of TR/MM and E failures were 2%, 5%, and 8% and 0.1%, 2%, and 3%, respectively. The median times to total ipsilateral, TR/MM, E, and contralateral failure were 6.5, 5.7, 7.4, and 5.2 years, respectively. Between 0 and 5 years of follow-up, E failures represented 7% of the total ipsilateral failures observed. From 5-10 and 10-15 years, E failures represented 39% and 27% of the total, respectively (p = 0.01). Contralateral failure was significantly more likely to occur in the first 5 years of follow-up than IBTR, accounting for 50 (63.3%) of the 79 failures in that interval (p = 0.02). No significant differences in survival rates were detected between any of the various failure types. On multivariate analysis, only reduced time to tumor recurrence was found to be adversely associated with overall survival., Conclusions: The rates and patterns of IBTR vary with time and, after 5 years, approach the rates of development of a contralateral breast cancer. E failures are, overall, less frequent than TR/MM but contribute increasingly to the IBTR rate after 5 years. Time to tumor recurrence is the most reliable predictor of prognosis after IBTR.

Purpose: We hypothesize that surgical clips placed in the biopsy cavity during lumpectomy can be used as radiographic markers to facilitate image-guided external beam accelerated partial breast irradiation., Methods and Materials: We evaluated 28 patients with surgically placed clips in the lumpectomy cavity and two CT scans on different days. To establish whether the clips remain predictive of the lumpectomy cavity throughout therapy, we analyzed the motion of both cavities with repeat volumetric CT scans. The three-dimensional (3D) locations of each lumpectomy cavity and the associated clips were defined as individual regions of interest (ROIs). A single point of interest (POI) was defined for each ROI. The calculated movements of the lumpectomy cavity POIs between different scans were compared to those of the clip POIs. The second CT data set was then moved in accordance to the calculated clip POI's movement. The volume of the (second) lumpectomy cavity associated with the second scan outside of the (first) cavity of the first scan was measured. In addition, the required amount of a radial margin expansion around the first lumpectomy cavity to ensure coverage of the second lumpectomy cavity both before and after moving the second lumpectomy according to the clip POI movement was calculated., Results: The two CT scans were obtained on average 27 days apart, and the mean lumpectomy size decreased from 35 to 16 cc. The clip and lumpectomy cavity POIs moved a mean of 3 mm along the three principal Cartesian axes. In moving the second lumpectomy cavity according to the clip POI displacement from its original position, the volume of the second lumpectomy cavity outside of the volume of the first decreased from 2.6 cc to 1.0 cc after correction, and the required radial margin on the first lumpectomy cavity to include the second lumpectomy cavity decreased from 5.5 mm vs. 3.8 mm., Conclusion: The surgically placed clips after lumpectomy are strong radiographic surrogates for the biopsy cavity. If the clips were used to guide accelerated partial breast irradiation, a planning target volume margin of the order of 5 mm could be used, significantly smaller than the 10-mm margin currently employed.

Purpose: We analyzed our experience treating localized prostate cancer to determine the impact of androgen deprivation (AD) on clinical outcome if administered at the time of isolated biochemical failure (BF) vs. after clinical failure (clinical failure), and the associated impact of various BF definitions., Methods: A total of 1,201 patients with stage T1-T3N0M0 prostate cancer were treated with external beam radiotherapy (EBRT) to a median dose of 66.6 Gy. Early AD was defined as administration of AD after BF, without evidence of clinical failure. Delayed AD was defined as administration of AD after clinical failure. Multiple BF definitions were tested for capacity to predict subsequent clinical failure. For each BF definition, outcome was compared for BF patients receiving early AD vs. no or delayed AD., Results: Five-year clinical failure (from date of BF) was 60% for patients who experienced a prostate-specific antigen rise to >/=3 ng/mL above nadir. For these patients, early AD was associated with decreased 5-year local failure (4% vs. 33%), distant metastasis (13% vs. 44%), cause-specific death (9% vs. 24%), and death due to any cause (32% vs. 48%), despite poorer prognostic factors in patients receiving early AD. On multivariate analysis, early AD remained independently significant for each of these end points., Conclusion: The efficacy of AD after BF varies depending on the BF definition. When an optimal BF definition is applied, early AD decreases distant metastasis and improves survival. Prostate-specific antigen elevation to >/=2 or >/=3 ng/mL above nadir seems optimal in establishing clinically significant BF and the timing of AD intervention.

Twelve patients with fracture of the distal radius were treated by open reduction and internal fixation with titanium minifragment plates. There were 8 women and 3 men, with a mean age of 42 years. The mean follow-up was 18 months. According to the score of Gartland and Werley, 11 patients had an excellent result and one patient had a good result. All patients reported no pain in their activities of daily living and were satisfied with the result. All workers returned to work. One patient developed reflex sympathetic dystrophy which resolved with treatment. No patients needed plate removal because of irritation of the tendons. The results obtained with this technique appear promising, although more cases are needed to achieve a definitive conclusion.

Purpose: The active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT)., Methods and Materials: Ten patients with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans., Results: The medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing., Conclusions: The dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment.

Purpose: We evaluated the potential for differing acute and chronic toxicities between 2 monotherapy methods of image guided conformal brachytherapy, high dose rate (HDR) brachytherapy alone and low dose rate (LDR) permanent palladium seeds., Materials and Methods: A total of 149 patients with biopsy proven, early stage prostate cancer were consecutively treated with interstitial brachytherapy as the sole method of treatment at William Beaumont Hospital between 1999 and 2001. Of the 149, 65 patients were treated with HDR using 192 iridium (192Ir), and 84 patients were treated with LDR using 103 palladium (103Pd). The majority of patients had clinical stage II, T1c or T2a disease, pretreatment prostate specific antigen less than 10 ng/ml and Gleason score 6 or less. Neoadjuvant hormones were used in 36% of patients for gland volume optimization. All treatments were performed transperineally with trans-rectal ultrasound guidance and fluoroscopy for verification of needle/seed positions. The HDR dose was 38 Gy delivered in 4 fractions, 2 times daily during 2 days. The LDR dose was 120 Gy. Acute and chronic toxicities were scored according to the Common Toxicity Criteria scale, version 2.0., Results: Median followup for all patients was 35 months. The 2 treatment groups were well-balanced with respect to age, clinical stage, prostate specific antigen, Gleason score, use of neoadjuvant hormones, pretreatment genitourinary symptoms, implanted gland volume and length of followup. Biochemical control (American Society for Therapeutic Radiology and Oncology definition) was 97% and 98% for LDR and HDR, respectively. HDR brachytherapy alone was associated with decreased acute rates of grade 1 to 3 dysuria (67% versus 36%, p <0.001), urinary frequency/urgency (92% versus 54%, p <0.001) and rectal pain (20% versus 6%, p = 0.017). These differences remained significant when patients who received prior hormonal therapy were excluded from analysis. Selected chronic toxicities were also decreased with HDR, including long-term urinary frequency and urgency, 32% (HDR) vs 56% (103Pd), p = 0.004. There were no differences in the rates of chronic dysuria, urinary incontinence, retention or hematuria. Urethral stricture rates were 8% in the HDR alone group vs 3% for 103 Pd (p = 0.177). The 3-year actuarial impotence rate was 45% for the LDR group and only 16% for HDR. The majority of complications were grade 1. No grade 4 toxicities were encountered in either group. HDR decreased treatment cost by 19%., Conclusions: While HDR (192 iridium) and LDR (103Pd) monotherapy maintained the same biochemical control, the use of HDR brachytherapy as monotherapy was associated with decreased rates of acute urinary frequency, urgency, dysuria and rectal pain compared to LDR. Chronic urinary frequency, urgency and grade 2 rectal toxicities were also decreased with HDR. A dramatic decrease (66%) was noted in the rate of sexual impotency with HDR. In addition, patients treated with HDR did not remain radioactive after treatment. There was a decrease in cost from not purchasing seeds per patient. HDR monotherapy as prostate cancer treatment resulted in the same biochemical control with much lower toxicity. It is an accepted, convenient, cost-effective method of prostate brachytherapy for patients with favorable risk prostate cancer.

Purpose: A CT-based three-dimensional (3D) method was used to analyze the intra- and interfraction reproducibility of lung immobilization during moderate deep inspiration breath hold (mDIBH), defined as 75% of the maximal inspiration using an active breathing control (ABC) apparatus., Methods and Materials: The ABC apparatus was used to immobilize the breathing motion with a computer-controlled valve. Immobilization of the lungs in breast cancer patients was used as a model to evaluate the reproducibility of mDIBH using the ABC apparatus. CT scans were acquired twice at mDIBH in the same session for 30 breast cancer patients. Twenty-three of them were immobilized with an alpha-cradle, of which 14 had a repeat scan at mDIBH 1-4 weeks later. Twelve of those patients received intensity-modulated radiotherapy to the left breast at mDIBH to displace the heart from the beam. The remaining patients were treated at free breathing, with either intensity-modulated irradiation to the whole breast or conformal partial breast irradiation. To remove the component of setup error, mDIBH scans were registered with respect to the vertebrae. The lungs and carina were auto-contoured to form 3D surfaces for each data set. The closest distance-to-agreement (DTA) for each point between the 3D surfaces of the corresponding CT scans was displayed on a 3D surface map. For analysis, each lung was divided along its inferior to superior extent into six regions, from the basal 10%, the next four consecutive 20% sections in height, to the last apical 10%. Likewise, the carina was divided into regions of the trachea and bifurcation. The mean and standard deviation (SD) of the DTA for each of these regions was computed., Results: With the patient positioned in an alpha-cradle, the mean +/- SD intrafraction DTA was 1.5 +/- 1.4 mm for the left lung and 1.0 +/- 1.4 mm for the right lung. The corresponding values without the use of an alpha-cradle were significantly greater, with 1.9 +/- 2.1 mm and 2.2 +/- 2.2 mm for the left and right lung, respectively (p <0.005 for the SD of the left lung and p <0.0003 for the SD of the right lung). The interfraction DTA for the left and right lungs was 1.4 +/- 1.7 mm and 1.4 +/- 1.6 mm, respectively. The regional analysis demonstrated better immobilization for the upper two-thirds of the chest wall compared with that for the lung base. The DTA values obtained for the tracheal bifurcation were 0.9 +/- 0.8 mm for intrafraction and 1.4 +/- 1.0 mm for interfraction., Conclusion: The ABC device can be used to reduce respiratory motion at mDIBH in breast cancer patients or those patients who can perform the maneuver. This device demonstrated excellent intra- and interfraction reproducibility of chest wall and carina immobilization, especially when combined with alpha-cradle immobilization. Internal margins for suspended breathing can be extrapolated from these data for various anatomic regions within the lung and chest wall.

Purpose: To report the long-term outcome for patients with Stage T1-T2 adenocarcinoma of the prostate definitively irradiated in the prostate-specific antigen (PSA) era., Methods and Materials: Nine institutions combined data on 4839 patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a pretreatment PSA level and had received >or=60 Gy as definitive external beam radiotherapy. No patient had hormonal therapy before treatment failure. The median follow-up was 6.3 years. The end point for outcome analysis was PSA disease-free survival at 5 and 8 years after therapy using the American Society for Therapeutic Radiology and Oncology (ASTRO) failure definition., Results: The PSA disease-free survival rate for the entire group of patients was 59% at 5 years and 53% at 8 years after treatment. For patients who had received >or=70 Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by the PSA criteria, 416 had local failure, and 329 had distant failure. The greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10 tumors for whom it was 6%. In multivariate analysis for biochemical failure, pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year were all significant prognostic factors. The length of follow-up and the effect of backdating as required by the ASTRO failure definition also significantly affected the outcome results. Dose effects were most significant in the intermediate-risk group and to a lesser degree in the high-risk group. No dose effect was seen at 70 or 72 Gy in the low-risk group., Conclusion: As follow-up lengthens and outcome data accumulate in the PSA era, we continue to evaluate the efficacy and durability of radiotherapy as definitive therapy for early-stage prostate cancer. Similar studies with higher doses and more contemporary techniques will be necessary to explore more fully the potential of this therapeutic modality.

Purpose: To systematically evaluate four different techniques of radiation therapy (RT) used to treat non-small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation., Methods and Materials: Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non-small-cell lung cancer using four different RT techniques to treat the primary lung tumor +/- the hilar/mediastinal lymph nodes: (1) Intensity-modulated radiation therapy (IMRT), (2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (3) Limited 3D-CRT using only 2 to 3 beams, and (4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and (18)fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either > or =1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to > or =99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V(20) < or =25%, mean lung dose < or =15 Gy, esophagus V(50) < or =25%, mean esophageal dose < or =25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses., Results: Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%-8% greater than 3D-CRT and 14%-16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V(20) was 36% with ENI vs. 23%-25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V(50) was doubled with ENI, to 34% rather than 15%-18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%-7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V(20) and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V(50) by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%-30% over 3D-CRT and 130%-140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V(20), mean dose, and NTCP in node-positive patients., Conclusion: The use of 3D-CRT, particul mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%-30% greater than 3D-CRT and 130%-140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.

Purpose: The aim of the study was to evaluate the 10-year treatment outcome of utilizing adjuvant high-dose whole abdominal irradiation (WAPI technique) with a pelvic/vaginal boost in patients with stage I-III endometrial carcinoma at high risk for intra-abdominopelvic recurrence, including serous-papillary and clear cell histologies., Material and Methods: In a prospective nonrandomized trial, 132 patients were treated with adjuvant WAPI between November 1981 and October 2001. Forty-three patients (32%) were 1998 FIGO stage I-II and 89 (68%) were stage III. Pathological features included the following: 66 (52%) with deep myometrial invasion, 50 (38%) with positive peritoneal cytology, 89 (67%) with high-grade lesions, 25 (19%) with positive pelvic/para-aortic lymph nodes, and 58 (45%) with serous-papillary or clear cell histology., Results: The mean follow up was 6.4 years (range 0.6-16.1). For the entire group, the 5- and 10-year cause-specific survival (CSS) was 77 and 72%, whereas the disease-free survival (DFS) was 55 and 45%. When stratified by histology the 5- and 10-year CSS for adenocarcinoma was 75 and 70%, while serous-papillary/clear cell was 80 and 74% (P = 0.314). The 5- and 10-year DFS for adenocarcinoma was 59 and 49%, whereas serous-papillary/clear cell was 49 and 38% (P = 0.563). For surgical stages I-II, the 5-year CSS was 83% for adenocarcinoma and 89% for serous-papillary (P = 0.353). For stage III, it was 73 and 62% (P = 0.318), respectively. Forty-six patients (35%) relapsed. The first site of failure was the abdomen/pelvis in 27/46 (59%). When stratified by histologic variant, 34% of patients with adenocarcinoma and 41% with serous-papillary developed recurrent disease. In multivariate regression analysis only advancing age was of prognostic significance for CSS (P = 0.025) and DFS (P = 0.026). Chronic grade 3/4 GI toxicity was seen in 14%, and 2% of patients developed grade 3 renal toxicity., Conclusion: High-dose adjuvant WAPI is very effective treatment with excellent 10-year results for stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including serous-papillary or clear cell histology. The low long-term complication rate with high CSS makes high-dose WAPI the treatment of choice for these patients with significant comorbidities.

Introduction: We present our initial clinical experience using moderate deep-inspiration breath hold (mDIBH) with an active breathing control (ABC) device to reduce heart dose in the treatment of patients with early-stage, left-sided breast cancer using external beam radiation therapy (EBRT) limited to the whole breast., Methods and Materials: Between February and August 2002, 5 patients with Stages I/II left-sided breast cancer received EBRT limited to the whole breast using an ABC device. After standard virtual simulation, patients with >2% of the heart receiving >30 Gy in free breathing were selected. All patients underwent a training session with the ABC apparatus to determine their ability to comfortably maintain mDIBH at 75% of the maximum inspiration capacity. Three patients received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4 Gy in 28 fractions. For each of the medial and lateral tangential beams, radiation was delivered during 2 or 3 breath hold durations that ranged from 18 to 26 s. "Step-and-shoot" intensity modulation was employed to achieve uniform dose distribution. Open beam segments were purposely delivered over 2 breath hold sessions and captured on electronic portal images to allow intra- and interfraction setup error analysis. All electronic portal images of the tangential beams were analyzed off-line using an in-house treatment verification tool to assess the anteroposterior, craniocaudal, and rotational uncertainties. Corrections were applied if necessary., Results: A comparison of treatment plans performed on breath-hold and free-breathing CTs showed that ABC treatments achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart V(30)) and 1.5% in the heart normal tissue complication probability. A total of 134 ABC treatment sessions were performed in the 5 patients. The average number of breath holds required per beam direction was 2.5 (4-6 per treatment) with a median duration of 22 s per breath hold (range: 10-26 s). Patients tolerated mDIBH well. The median treatment time was 18.2 min (range: 13-32 min), which was progressively shortened with increasing experience. A total of 509 portal images were analyzed. Combining measurements for all patients, the interfraction setup errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4 mm, 3.2 mm, and 1 degrees, respectively, for the medial beam and 2.3 mm, 3.1 mm, and 1 degrees, respectively, for the lateral beam. For all patients, the intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD)., Conclusion: Reduction in heart V(30) can be achieved in patients with left-sided breast cancer using mDIBH assisted with an ABC device. With increasing experience, ABC treatments were streamlined and could be performed within a 15-min treatment slot. Our results suggest that mDIBH using an ABC device may provide one of the most promising methods of improving the efficacy of EBRT in patients with left-sided breast cancer, particularly when wide tangential beams are employed. Breast cancer; Breath hold; Radiation therapy; Intensity modulated radiation therapy

Purpose: To evaluate the heart and lung sparing effects of moderate deep inspiration breath hold (mDIBH) achieved using an active breathing control (ABC) device, compared with free breathing (FB) during treatment with deep tangents fields (DT) for locoregional (LR) irradiation of breast cancer patients, including the internal mammary (IM) nodes (IMNs). To compare the DT-mDIBH technique to other standard techniques and to evaluate the dosimetric effect of intensity-modulated radiation therapy (IMRT)., Methods and Materials: Fifteen patients (9 left-sided and 6 right-sided lesions) with Stages 0-III breast cancer underwent standard FB and ABC computed tomographic (CT) scans in the treatment position. A dosimetric planning study was performed. In FB, the 9 left-sided patients were planned with a 5-field technique where electron fields covering the IM region were matched to shallow tangents using wedges (South West Oncology Group [SWOG] protocol S9927 technique A). This method was compared with a 3-field DT technique covering the breast and the IMNs (SWOG S9927 technique B). Compensation with IMRT was then compared with wedges for each technique. For the 15 total patients, dosimetric planning using DT with IMRT was then reoptimized on the mDIBH CT data set for comparison. Dose-volume histograms for the clinical target volume (CTV) (including the IMNs), planning target volume (PTV), ipsilateral and contralateral breast, and organs at risk (OAR) were analyzed. In addition, normal tissue complication probabilities (NTCP) for lung and heart, mean lung doses, and the number of monitor units (MUs) for a 1.8 Gy fraction were compared., Results: For the 9 left-sided patients, the mean percentage of heart receiving more than 30 Gy (heart V30) was lower with the 5-field wedged technique than with the DT wedged technique (6.8% and 19.1%, respectively, p < 0.004). For the DT technique, the replacement of wedges with IMRT slightly diminished the mean heart V30 to 16.3% (p < 0.51). The introduction of mDIBH to the DT-IMRT technique reduced the heart V30 by 81% to a mean of 3.1% (p < 0.0004). Compared with 5-field IMRT, DT-IMRT with mDIBH reduced the heart V30 for 6 of the 9 patients, entirely avoiding heart irradiation in 2 of these 6 patients. For DT-IMRT, mDIBH reduced the mean lung dose and NTCP to levels obtained with the 5-field IMRT technique. For the 15 patients planned with DT-IMRT in FB, the use of mDIBH reduced the mean percentage of both lungs receiving more than 20 Gy from 20.4% to 15.2% (p < 0.00007). With DT-IMRT, more than 5% of the contralateral breast received more than 10 Gy for 6 of the 9 left-sided patients in FB, 3 of those 9 patients in mDIBH, and only 1 of those 9 patients planned with 5 fields. The mean % of the PTV receiving more than 55 Gy (110% of the prescribed dose) was 36.4% for 5-field wedges, 33.4% for 5-field IMRT, 28.7% for DT-wedges, 12.5% for DT-IMRT, and 18.4% for DT-IMRT mDIBH. The CTV remained covered by the 95% isodose in all the DT plans but one (99.1% of the volume covered). DT-wedges required more MUs than DT-IMRT (mean of 645 and 416, respectively, p < 0.00004)., Conclusion: mDIBH significantly reduces heart and lung doses when DT are used for LR breast irradiation including the IMNs. Compared with shallow tangents matched with electrons, DT with mDIBH reduces the heart dose (in most patients) and results in comparable lung toxicity parameters, but may increase the dose to the contralateral breast. IMRT improves dose homogeneity, slightly reduces the dose to the heart, and diminishes the number of MUs required.

Purpose: We present a novel three-dimensional conformal radiation therapy (3D-CRT) technique to treat the lumpectomy cavity, plus a 1.5-cm margin, in patients with early-stage breast cancer and study its clinical feasibility., Methods and Materials: A 3D-CRT technique for partial-breast irradiation was developed using archived CT scans from 7 patients who underwent an active breathing control study. The clinical feasibility of this technique was then assessed in 9 patients who were prospectively enrolled on an Investigational Review Board-approved protocol of partial-breast irradiation. The prescribed dose was 34 Gy in 5 patients and 38.5 Gy in 4 patients, delivered in 10 fractions twice daily over 5 consecutive days. The impact of both breathing motion and patient setup uncertainty on clinical target volume (CTV) coverage was studied, and an appropriate CTV-to-PTV (planning target volume) margin was calculated., Results: By adding a CTV-to-PTV "breathing-only" margin of 5 mm, 98%-100% of the CTV remained covered by the 95% isodose surface at the extremes of normal inhalation and normal exhalation. The "total" CTV-to-PTV margin employed to accommodate organ motion and setup error (10 mm) was found to be sufficient to accommodate the observed uncertainty in the delivery precision. Patient tolerance was excellent, and acute toxicity was minimal. No skin changes were noted during treatment, and at the initial 4-8-week follow-up visit, only mild localized hyperpigmentation and/or erythema was observed. No instances of symptomatic radiation pneumonitis have occurred., Conclusions: Accelerated partial-breast irradiation using 3D-CRT is technically feasible, and acute toxicity to date has been minimal. A CTV-to-PTV margin of 10 mm seems to provide coverage for most patients. However, more patients and additional studies will be needed to validate the accuracy of this margin, and longer follow-up will be needed to assess acute and chronic toxicity, tumor control, and cosmetic results.

Purpose: The clinical significance of pretreatment biopsy characteristics is not well understood relative to known prognostic factors. We performed a complete pathology analysis of pretreatment biopsy specimens in an attempt to clarify their impact on clinical outcome following radiotherapy., Materials and Methods: From 1991 to 1999, 160 patients with locally advanced prostate cancer were prospectively treated with external beam radiotherapy in combination with high dose rate brachytherapy at our hospital and had pretreatment biopsy material available for complete pathological review. Patients with pretreatment prostate specific antigen (PSA) 10.0 ng./ml. or greater, Gleason 7 or greater or clinical stage T2b-T3c N0 M0 disease were eligible for study entry. Pelvic external beam radiotherapy (46.0 Gy.) was supplemented with 3 (1991 to 1995) or 2 (1995 to 1999) ultrasound guided transperineal interstitial iridium high dose rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy. per implant. All pretreatment biopsy specimen slides from each case were reviewed by a single pathologist (N. S. G.). Median followup was 4.2 years. Biochemical failure was defined as 3 consecutive PSA increases., Results: On univariate analysis pretreatment PSA, Gleason score, clinical T classification, percentage of positive biopsy cores, dose per implant and total radiotherapy dose (equivalent in 2 Gy. fractions) were significantly associated with biochemical failure. Perineural invasion was of borderline significance (p = 0.07). On univariate analysis for clinical failure only Gleason score and percent positive cores were significant. Percent positive cores was associated with biochemical and clinical failure whether analyzed in subgroups or as a continuous variable. Patients with less than 33% positive cores had a 5-year biochemical control rate of 83% and 5-year clinical failure rate of only 7%. Conversely, patients with more than 67% positive cores had a 5-year biochemical control rate of only 57% and 25% had clinical failure at 5 years. Since percent positive cores correlated with biochemical and clinical failure, an analysis was performed to determine which other prognostic factors were associated with percent positive cores. Pretreatment PSA level, Gleason score, clinical T classification and perineural invasion were significantly associated with a higher percent positive cores. Nevertheless, on Cox multiple regression analysis higher percent positive cores, pretreatment PSA and Gleason score remained independently associated with biochemical failure but not T classification. On Cox multiple regression analysis for clinical failure only Gleason score remained independently significant with percent positive cores maintaining borderline significance (p = 0.07)., Conclusions: Percent positive pretreatment biopsy cores is a powerful predictor of biochemical and clinical outcome for prostate cancer treated with radiotherapy, independent of other known prognostic factors. Percent positive cores should be seriously considered as a primary factor in risk group stratification for prostate cancer.

Purpose: To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features., Methods and Materials: In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings., Results: The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p = 0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p = 0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p = 0.480). For Stage III, it was 75% and 57%, respectively (p = 0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most failures for either histologic group occurred within the abdominopelvic region. However, one-third of the adenocarcinoma recurrences were in the lung. Multivariate regression analysis (age, surgical stage, grade, myometrial invasion, histologic type, lymph node status, and peritoneal cytology) demonstrated age (p = 0.019) and surgical stage (p = 0.036) to be of prognostic significance for CSS; age (p = 0.036) was the only significant prognostic factor for DFS. Grade 1-2 gastrointestinal and hematologic acute toxicities were common. Asymptomatic bibasilar scarring on chest X-ray and mild elevation of liver enzymes were seen in almost 50% of the patients. Even though chronic toxicities were less frequent, 12% developed Grade 3-4 gastrointestinal and 2% Grade 3 renal toxicities., Conclusion: Adjuvant WAPI is very effective treatment with excellent 10-year results for Stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including SP or CC histologic variants, deep myometrial invasion, high grade, nodal involvement, and positive peritoneal cytology. The low long-term complication rate with high CSS rate makes WAPI the treatment of choice for these patients with significant comorbidities.

Purpose: The clinical significance of postradiotherapy (RT) prostate biopsy characteristics is not well understood relative to the known prognostic factors. We performed a detailed pathologic review of posttreatment biopsy specimens in an attempt to clarify their relationship with clinical outcome and radiation dose., Methods and Materials: Between 1991 and 1998, 78 patients with locally advanced prostate cancer were prospectively treated with external beam RT in combination with high-dose-rate brachytherapy at William Beaumont Hospital and had post-RT biopsy material available for a complete pathologic review. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen level > or =10.0 ng/mL, Gleason score > or =7, or clinical Stage T2b-T3cN0M0. Pelvic external beam RT (46.0 Gy) was supplemented with three (1991-1995) or two (1995-1998) ultrasound-guided transperineal interstitial (192)Ir high-dose-rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Post-RT prostate biopsies were performed per protocol at a median interval of 1.5 years after RT. All pre- and post-RT biopsy specimen slides from each case were reviewed by a single pathologist (N.S.G.). The presence and amount of residual cancer, most common RT-effect score, and least amount RT-effect score were analyzed. The median follow-up was 5.7 years. Biochemical failure was defined as three consecutive prostate-specific antigen rises., Results: Forty patients (51%) had residual cancer in the post-RT biopsies. The 7-year biochemical control rate was 79% for patients with negative biopsies vs. 62% for those with positive biopsies with marked RT damage vs. 33% for those with positive biopsies with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores (p = 0.01), lower total RT dose (p = 0.001), lower dose per implant (p = 0.001), and greater percentage of positive post-RT biopsy cores (p = 0.01) were each associated with biochemical failure (Cox regression, univariate analysis). For patients with <25% positive post-RT biopsy cores, the 7-year biochemical control rate was 81% vs. a 62% biochemical control rate for those with 25-49% positive cores and only 32% for those with > or =50% positive cores (p = 0.01). On Cox multiple regression analysis, only the percentage of positive pre-RT biopsy cores and RT dose remained significantly associated with biochemical failure. Of all the factors analyzed, only the pretreatment cancer volume and lower RT dose were significantly associated with residual cancer and/or residual cancer with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.04). A lower total RT dose was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.02). For patients who received <80 Gy (equivalent in 2-Gy fractions), 73% had positive post-RT biopsies vs. a 56% biopsy positivity rate for those who received 84-90 Gy and only 39% for those who received > or =92 Gy (p = 0.07)., Conclusion: Patients with positive post-RT biopsies are more likely to experience biochemical failure, especially when the RT damage is minimal. Patients who have a larger pretreatment tumor volume or receive a lower RT dose are more likely to demonstrate post-RT biopsy positivity and biochemical failure.

Purpose: Geometric uncertainties in the process of radiation planning and delivery constrain dose escalation and induce normal tissue complications. An imaging system has been developed to generate high-resolution, soft-tissue images of the patient at the time of treatment for the purpose of guiding therapy and reducing such uncertainties. The performance of the imaging system is evaluated and the application to image-guided radiation therapy is discussed., Methods and Materials: A kilovoltage imaging system capable of radiography, fluoroscopy, and cone-beam computed tomography (CT) has been integrated with a medical linear accelerator. Kilovoltage X-rays are generated by a conventional X-ray tube mounted on a retractable arm at 90 degrees to the treatment source. A 41 x 41 cm(2) flat-panel X-ray detector is mounted opposite the kV tube. The entire imaging system operates under computer control, with a single application providing calibration, image acquisition, processing, and cone-beam CT reconstruction. Cone-beam CT imaging involves acquiring multiple kV radiographs as the gantry rotates through 360 degrees of rotation. A filtered back-projection algorithm is employed to reconstruct the volumetric images. Geometric nonidealities in the rotation of the gantry system are measured and corrected during reconstruction. Qualitative evaluation of imaging performance is performed using an anthropomorphic head phantom and a coronal contrast phantom. The influence of geometric nonidealities is examined., Results: Images of the head phantom were acquired and illustrate the submillimeter spatial resolution that is achieved with the cone-beam approach. High-resolution sagittal and coronal views demonstrate nearly isotropic spatial resolution. Flex corrections on the order of 0.2 cm were required to compensate gravity-induced flex in the support arms of the source and detector, as well as slight axial movements of the entire gantry structure. Images reconstructed without flex correction suffered from loss of detail, misregistration, and streak artifacts. Reconstructions of the contrast phantom demonstrate the soft-tissue imaging capability of the system. A contrast of 47 Hounsfield units was easily detected in a 0.1-cm-thick reconstruction for an imaging exposure of 1.2 R (in-air, in absence of phantom). The comparison with a conventional CT scan of the phantom further demonstrates the spatial resolution advantages of the cone-beam CT approach., Conclusions: A kV cone-beam CT imaging system based on a large-area, flat-panel detector has been successfully adapted to a medical linear accelerator. The system is capable of producing images of soft tissue with excellent spatial resolution at acceptable imaging doses. Integration of this technology with the medical accelerator will result in an ideal platform for high-precision, image-guided radiation therapy.

Purpose: The posttreatment prostate-specific antigen (PSA) profile can often be difficult to interpret after external beam radiotherapy for prostate cancer. We performed an extensive analysis of post-radiotherapy PSA measurements to determine the clinical significance of biochemical failure (BF) and the correlation of BF with clinical failure (CF) and cause-specific death (CSD)., Materials and Methods: Between 1987 and 1997, 727 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with definitive external beam radiotherapy at William Beaumont Hospital and had at least five post-radiotherapy PSA levels and did not receive hormonal therapy for post-radiotherapy PSA elevations only (before evidence of CF). All patients received external beam radiotherapy alone (no adjuvant hormonal therapy) to a median total prostate dose of 66.6 Gy. More than 20 BF definitions were tested for their correlation with CF (any local failure or distant metastasis) and CSD. All BF definitions were tested for sensitivity, specificity, accuracy, and positive and negative value of predicting subsequent CF and CSD. The median follow-up was 5.0 years., Results: Three consecutive PSA rises yielded a 73% sensitivity, 76% specificity, and 75% overall accuracy for predicting CF. The 10-year CF rate (from the completion of radiotherapy) for those 251 patients demonstrating three consecutive rises (BF) was 64% vs. 14% for those patients who did not have three rises (biochemically controlled). Defining BF as a post-nadir increase to >or=3 ng/ml above the nadir yielded the highest accuracy of 87%. In addition, this definition also seemed to provide the greatest separation in CF rates: 82% for BF vs. 5% for biochemically controlled at 10 years after radiotherapy. CF rates were also calculated from the date of BF (e.g., date of third rise). The CF rates at 6 months and 2 years after the third PSA rise were 9% and 27%, respectively. The CF rates at 6 months and 2 years after an increase to >or=3 ng/ml above the nadir were 23% and 54%, respectively. Once a patient was classified as a BF, regardless of the BF definition, the CF rate varied markedly, depending on the pretreatment characteristics. For each BF definition, younger age at diagnosis, higher pretreatment PSA, and higher Gleason score independently predicted for CF after BF on Cox multiple regression analysis. For instance, patients with a pretreatment PSA <4.0 ng/ml demonstrated an 11% CF rate at 2 years after the third PSA rise vs. 46% after three rises with a pretreatment PSA >or=20.0 ng/ml. Similarly, patients with Gleason 2-4 had a 2-year CF rate of only 3% after a nadir >or=1.0 ng/ml vs. 47% for Gleason 8-10 at 2 years after a nadir >or=1.0 ng/ml. Although the CF rate also coincided with pretreatment characteristics when using >or=3 ng/ml above the nadir, CF rates remained high even for low-risk patients (e.g., 2-year CF of 48% for PSA <10.0 ng/ml, 41% for Gleason 2-4). In addition, a shorter time interval from nadir to nadir + 1 ng/ml or from nadir to nadir + 3 ng/ml (corresponding to a steeper slope in the PSA profile) independently predicted for CF., Conclusion: Once the post-radiotherapy PSA profile reaches >or=3 ng/ml above the nadir, there is a high risk of clinical failure within a relatively short time period, for which treatment intervention may be considered, regardless of pretreatment characteristics. After a nadir >or=1.0 ng/ml or three consecutive rises, some patients (especially with low-risk pretreatment characteristics) may be considered for further PSA observation before treatment intervention.

We studied relationships among clinicopathologic factors in 78 patients with unfavorable prostate adenocarcinoma treated in a dose-escalation radiation therapy (RT) study using pre- and 18-month protocol post-RT biopsy specimens. Pre-RT factors analyzed were serum prostate-specific antigen (PSA) level, Gleason score, and percentage of needle cores with adenocarcinoma; post-RT factors were percentage of needle cores with adenocarcinoma and amount of radiation effect on the adenocarcinoma. Of 78 patients, 42 (54%) had residual adenocarcinoma in the post-RT biopsy specimen. Lower total RT dose and dose per implant and greater serum PSA level were associated with an increasing percentage of needle cores with residual post-RT adenocarcinoma. Lower RT dose, an increasing percentage of pre-RT needle cores with adenocarcinoma, and a greater serum PSA level were associated with an increasing percentage of post-RT needle cores with no to moderate RT effect scores in adenocarcinoma. The mean percentage of pre-RT and post-RT needle cores with adenocarcinoma was greater in patients with post-RT biopsy specimens with no to moderate RT effect. The percentage of pre-RT needle cores with adenocarcinoma (a surrogate marker of adenocarcinoma volume), serum PSA level, and RT dose are the key components in the dose-response relationship. Gleason score and gland volume did not contribute significantly to this relationship.

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed., Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure., Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%., Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Purpose: To demonstrate a new interactive Internet-ready database for prospective clinical trials in high-dose-rate (HDR) brachytherapy for prostate cancer., Methods and Materials: An Internet-ready database was created that allows common data acquisition and statistical analysis. Patient anonymity and confidentiality are preserved. These data forms include all common elements found from a survey of the databases. The forms allow the user to view patient data in a view-only or edit mode. Eight linked forms document patient data before and after receiving HDR therapy. The pretreatment forms are divided into four categories: staging, comorbid diseases, external beam radiotherapy data, and signs and symptoms. The posttreatment forms separate data by HDR implant information, HDR medications, posttreatment signs and symptoms, and follow-up data. The forms were tested for clinical usefulness., Conclusion: This Internet-based database enables the user to record and later analyze all relevant medical data and may become a reliable instrument for the follow-up of patients and evaluation of treatment results.

Purpose: A new device has been developed with the goal of making breast-conserving therapy more widely available, by making breast brachytherapy as monotherapy simpler and more accurate. This is the first published report on the dosimetric characteristics of this device., Materials and Methods: The experience of a single institution participating in a multi-institutional trial is reported. Twelve patients were enrolled, of whom 8 were treated. Computed tomography scans of all 12 patients were obtained before initiation of treatment. A commercial three-dimensional planning system was used for retrospective detailed analysis of dosimetry, including dose-volume histograms and, in selected patients, skin dose distributions. These data were compared to those of a similar group of patients, analyzed previously, that was treated with interstitial high-dose-rate brachytherapy., Results: Compared with interstitial brachytherapy, the MammoSite device resulted in a treatment dose that was less uniform, with a mean dose homogeneity index of 0.77 vs. 0.93. Coverage and reproducibility were improved, with a mean D90 (minimum dose to 90% of target volume) of 90.0% of prescribed dose (SD 0.5, range: 89.2-90.8%) vs. 69.8% (SD 7.3, range: 61.1-83.5%) for interstitial brachytherapy., Conclusions: Reproducible placement was easily achieved in this very early experience, indicating a much smaller "learning curve" than for interstitial brachytherapy. Because skin doses can be increased with the use of this device, caution is indicated, although simple maneuvers can significantly reduce skin dose.

Purpose: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship., Methods and Materials: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals., Results: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50-60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy (V15) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity., Conclusions: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy for rectal carcinoma.

Purpose: A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low alpha/beta ratio), more typical of the surrounding late-responding normal tissue., Methods and Materials: Earlier estimates of alpha/beta for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, length of follow-up, and age., Results: The estimated value of alpha/beta from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This alpha/beta value is considerably less than typical values for tumors (> or =8 Gy), and more comparable to values in surrounding late-responding normal tissues., Conclusions: This analysis provides strong supporting evidence that alpha/beta values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced.

Between 1995 and 1999, 46 acute nonpathological humeral shaft fractures were treated with retrograde Marchetti-Vicenzi humeral nailing. The mean healing time of all fractures was 10.8 weeks. Forty-five fractures (97.9%) united primarily, and one needed bone grafting (2.1%). Function of the shoulder was excellent in 35 patients (76.1%) and moderate in 11 (23.9%). Elbow function was also excellent in 35 patients and moderate in 11. Global functional results were excellent in 16 patients (34.8%), good in 22 (47.8%) and fair in 8 (17.4%). There were 4 cases of 10 degrees varus malunion (8.6%), one case of 15 degrees varus malunion (2.1%), and one case of 15 degrees anterior angulation malunion (2.1%). These malunions were clinically well tolerated. Four patients required removal of the nail because of posterior elbow pain. Retrograde Marchetti-Vicenzi nailing is an acceptable alternative for the treatment of acute humeral shaft fractures with a low complication rate.

Purpose: Data were reviewed addressing the association between radiation therapy (RT) dose and treatment outcome for localized prostate cancer to help clarify the existence of a potential dose-response relationship., Methods and Materials: Articles were identified through the MEDLINE database, CancerLit database, and reference lists of relevant articles. Studies were categorized into four groups based upon the endpoint analyzed, including biochemical control (BC), local control (LC), pathologic control (PC), and cause-specific survival (CSS). The impact of increasing RT dose with each endpoint was recorded., Results: Twenty-two trials involving a total of 11,297 patients were identified. Of the 11 trials addressing the association of RT dose with LC, 9 showed statistically significant improvements. Of the 12 trials that reported BC with RT dose, all showed statistically significant improvements. Two out of 4 studies analyzing PC with increasing dose showed a positive correlation. Finally, 3 out of 9 studies addressing RT dose with CSS showed statistically significant improvements. Despite inconclusive results, patients with poor risk features (e.g., prostate-specific antigen [PSA] > or = 10, Gleason score [GS] > or = 7, or tumor stage > or = T2b) were most likely to benefit from increasing dose with respect to each endpoint. However, the optimal RT dose and the magnitude of benefit of dose escalation could not be identified., Conclusions: Although RT dose appears to correlate with various measures of treatment outcome, objective, high-quality data addressing this critical issue are still lacking. At the present time, the absolute improvement in outcome due to dose escalation, the subset of patients benefitting most, and the optimal dose remain to be defined.

Purpose: The rectal dose/volume relationship and inherent variations thereof are fundamental parameters to guide dose escalation in prostate cancer treatment. This study evaluates the effect of rectal dose/volume variation on the risk of rectal complication for different planning target volume (PTV) constructions., Methods and Materials: Thirty prostate patients with multiple daily CT scans obtained during the treatment course were included in this retrospective study. The dose distribution was calculated based on the pretreatment CT image alone. Treatment plans were generated by applying the four-field-box beam arrangement to each of three different PTVs: PTVs with 0.5-cm and 1.0-cm uniform margins, and a patient-specific PTV constructed using treatment imaging feedback. For each of the 30 patients, the rectal wall as manifested on each of multiple CT images was delineated after image bony registration to the pretreatment CT image, and applied to the corresponding treatment plan to obtain the rectal wall dose-volume histogram (DVH). Interpatient and intrapatient rectal dose/volume variations were quantified accordingly. The corresponding uncertainty and sensitivity of the risk of rectal complication to the variations were evaluated for each of the three PTVs. Finally, the efficacy of using multiple CT images to reduce uncertainty in planning evaluation was examined., Results: Sensitivity of the risk of rectal complication to rectal dose/volume variation strongly depends on the clinical target volume (CTV)-to-PTV margin or prescription dose, or both. Compared to the conventional two-dimensional (2D) prostate cancer treatment, the sensitivity for a conformal treatment can be 3 times higher or more. Due to the interpatient rectal dose/volume variation, the individual normal tissue complication probability (NTCP) was distributed from 10% to 37% when a common prescription dose was applied for all patients. The intrapatient rectal dose/volume variation introduces at least +/- 25% uncertainty in the NTCP calculation for at least 10% or 25% of the patients treated with the PTV of 1.0- or 0.5-cm margin, respectively. These uncertainties were larger for the smaller PTV, with the standard deviation up to 20%. By applying multiple CT image feedback, the NTCP uncertainty could be reduced by a factor of 2., Conclusions: Shape and position variation of rectum has less influence on treatment planning in the conventional 2D treatment of prostate cancer. However, this influence is quickly growing with high treatment dose or small CTV-to-PTV margins. To reduce the variation and uncertainties in the treatment planning evaluation associated with the inter- and intrapatient rectal dose/volume variation, the iso-NTCP model and treatment image feedback technique can be applied in dose escalation trials of prostate cancer treatment.

Purpose: Advances in technology allow the creation of complex treatment plans with tightly conforming doses. However, variations in positioning of the organ/patient with respect to treatment beams necessitate the use of an appreciable margin, potentially limiting dose escalation in many patients. To (1) reduce this margin and (2) test the hypothesis that the achievable level of dose escalation is patient dependent, a patient-specific, confidence-limited planning target volume (cl-PTV) was constructed using an adaptive radiotherapy (ART) process for prostate cancer treatment developed in-house. The potential dose escalation achievable with this ART process is quantified for both conformal radiotherapy (CRT) delivery and intensity-modulated radiotherapy (IMRT) delivery., Material and Methods: Patients with organ confined prostate cancer were entered prospectively into an ART process developed in-house. This ART process has been designed to improve accuracy and precision of dose delivery, consequently enhancing dose escalation. In this process, a cl-PTV is constructed for each patient in the second week of treatment based upon on-line portal and CT images acquired during the first week of treatment. The treatment prescription dose, defined as the minimum dose to the cl-PTV, is selected based on predefined dose-volume constraints for rectum/bladder and derived from the pretreatment planning CT image. In addition, the treatment modality (CRT or IMRT) is determined based on the level of dose escalation achievable and the risk of inaccurate targeting. The potential for both dose escalation and the application of IMRT was evaluated by comparing the prescription doses delivered using the ART process, with the cl-PTV, to those in the traditional treatment process, with a conventional generic PTV. In addition, the distributions of potential geometric target underdosing and normal tissue overdosing were also calculated to evaluate the quality of the conventional treatment plans., Results: One hundred and fifty patients have been treated with the ART process. When compared to the treatment dose delivered with the conventional treatment process (generic PTV), an average 5% (2.5--10%) more dose could be delivered using the ART process with CRT, and 7.5% (2.5--15%) more dose could be delivered with IMRT. Of the 150 patients, 70% were treated to a minimum cl-PTV dose > or = 77.4 Gy (81.3 Gy ICRU isocenter dose). Dosimetric analysis revealed that 81 Gy to the cl-PTV (or 86.7 Gy ICRU) could be prescribed to at least 50% of patients if IMRT was applied using the ART process. In contrast, IMRT did not yield an obvious dose escalation gain if patients were treated using the generic PTV. Our results also demonstrate that the cl-PTV is significantly smaller than the conventional generic PTV for most patients, with a mean volume reduction of 24% (range, 5--43%)., Conclusion: These results support our hypothesis that the achievable level of dose escalation using ART is patient dependent. By using the ART process to develop a cl-PTV, one can (1) optimize the dose level, (2) increase the applicability of IMRT, and (3) improve the quality of dose delivery. The ART process provides the foundation to identify a suitable option (CRT or IMRT) for the delivery of a safe treatment and dose escalation. It is now our standard of practice for prostate cancer treatment.