Faculty Bibliography

PURPOSE/OBJECTIVE: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/METHODS: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/CONCLUSIONS: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.

BACKGROUND:The objective of the current study was to provide descriptive information on a representative national sample of patients with prostate carcinoma who were treated with prostate brachytherapy (PB) in calendar year 1999. METHODS:A random survey was conducted by the Patterns of Care Study in radiation oncology of 59 facilities (1 facility had no eligible patients) that treated patients with prostate carcinoma in 1999 in the United States. A weighted sample size of 36,496 patients with prostate cancer was included in the 1999 survey (unweighted sample size, 554 patients). The main measures were the clinical characteristics of men prior to treatment and the technical characteristics of PB. Patients were classified into three prognostic groups according to T stage, pretreatment prostate specific antigen (PSA) level, and Gleason score. RESULTS:A weighted sample size of 13,293 patients (36%; unweighted sample size, 162 patients) was treated with PB. Compared with a weighted sample size of 23,203 patients (64%; unweighted sample size, 392 patients) was treated with external beam radiotherapy (EB), patients who received PB were significantly younger (mean age: PB group, 67.7 years; EB group, 70.8 years; P = 0.0006). The mean pretreatment PSA level for the PB group was lower compared with the EB group (9.9 ng/mL vs. 13.33 ng/mL; P = 0.0015). The prognostic groupings were more favorable for patients in the PB group compared with patients in EB group (P = 0.0365). The utilization of androgen deprivation therapy (ADT) in the PB group was similar to the utilization of ADT in the EB group (40.4% vs. 51.3%; P = 0.2282). The vast majority of men who were treated with PB received low-dose-rate, permanent sources (89%). Fifty-four percent of men received PB monotherapy (PBM), and the remaining 46% were treated with EB in addition to PB (EBPB). The prognostic groupings were more favorable for patients in the PBM group compared with patients in the EBPB group (P = 0.0037). Of the men who were treated with low-dose-rate PB, 59% were treated with iodine-125 (I-125), and 41% were treated with palladium-103 (Pd-103). I-125 was used more frequently in men who were treated with PBM, and Pd-103 was used more frequently in men who were treated with EBPB. Postimplantation dosimetry was documented in 61.0% of men who were treated with low-dose-rate PB. Computed tomography imaging was used for 46.5% of men. CONCLUSIONS:PB was used in 36% of men who were treated with radiotherapy nationally. The mean age of men who were treated with PB was younger than the population of men who were treated with EB alone. Nearly 50% of men who received PB also received EB. EB was used more frequently in men with higher-risk disease. ADT was used in 40% of patients in the PB group. Techniques and prescription doses were consistent with published guidelines.

PURPOSE/OBJECTIVE:We report the long-term prostate specific antigen relapse-free survival rates and predictors of biochemical outcome for patients 60 years or younger with prostate cancer treated with high dose conformal external beam radiotherapy. MATERIALS AND METHODS/METHODS:We retrospectively reviewed the records of 740 patients with prostate cancer treated with 3-dimensional conformal radiotherapy or intensity modulated external beam radiotherapy. Patients who also received androgen deprivation therapy were excluded from this analysis. Median radiation dose was 75.6 Gy and median followup was 88 months with a minimum followup of 24 months. Median followup for patients 60 years or younger in this report was 54 months (range 24 to 132). Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. RESULTS:Biochemical failure developed in 20 (21%) of the 96 men 60 years or younger, which was similar to the 22% failure rate observed in 644 patients older than 60. The 5 and 7-year biochemical disease-free survival rates were 82% and 79% in younger men, and 79% and 78% in older men, respectively (p = 0.48). For younger patients who received 81 Gy or greater, the 7-year prostate specific antigen relapse-free survival rates for favorable, intermediate and unfavorable risk patients were 96%, 87% and 50%, respectively. Multivariate analysis revealed that among patients 60 years or younger the most important predictor of biochemical relapse was radiation doses less than 75.6 Gy followed by Gleason score greater than 7. CONCLUSIONS:Men with prostate cancer 60 years or younger treated with high dose radiotherapy have an excellent biochemical outcome and fare as well as older patients. The use of conventional dose levels in patients 60 years or younger was associated with an 8-fold increase in the biochemical relapse rate and these doses should not be considered appropriate for the treatment of localized prostate cancer.

The relative inability of conventional radiotherapy to control localized prostate cancer results from resistance of subpopulations of tumor clonogens to dose levels of 65 to 70 Gy, the maximum feasible with traditional two-dimensional (2D) treatment planning and delivery techniques. Several technological advances have enhanced the precision and improved the outcome of external-beam radiotherapy. The three-dimensional conformal radiotherapy (3D-CRT) approach has permitted significant increases in the tumor dose to levels beyond those feasible with conventional techniques. Intensity-modulated radiotherapy (IMRT), an advanced form of conformal radiotherapy, has resulted in reduced rectal toxicity, permitting tumor dose escalation to previously unattainable levels with a concomitant improvement in local tumor control and disease-free survival. The combination of androgen deprivation and conventional-dose radiotherapy, tested mainly in patients with locally advanced disease, has also produced significant outcome improvements. Whether androgen deprivation will preclude the need for dose escalation or whether high-dose radiotherapy will obviate the need for androgen deprivation remains unknown. In some patients, both approaches may be necessary to maximize the probability of cure. In view of the favorable benefit-risk ratio of high-dose IMRT, the design of clinical trials to resolve these critical questions is essential.

The purpose of this study was to prospectively evaluate intraoperative prostatic edema during prostate brachytherapy with real-time ultrasound imaging and assess its impact upon the postimplant dosimetry of computer-optimized intraoperatively planned patients. Fifty consecutive patients with early-stage favorable risk adenocarcinoma of the prostate underwent transperineal ultrasound-guided I125 brachytherapy. Ultrasound volume studies of the prostate were performed immediately before and after placement of brachytherapy needles in the operating room. Twenty-five patients underwent intraoperative computer-optimized treatment planning using a genetic algorithm. Twenty-five patients underwent preimplant ultrasound studies for preimplant treatment planning. Postimplant dosimetry was performed on computed tomography scans obtained after the implant. Statistical analysis was performed taking into account patient age, preneedle volume, increase in intraoperative edema, use of hormonal therapy, type of isotope, number of needles or seeds used, and seed activity. For the intraoperatively planned patients, a median increase of 30% in intraoperative volume was found for the entire group. No correlation between the extent of intraoperative edema and %D90 (percentage of prescribed dose that covers 90% of the target volume) was found. None of the other analyzed variables correlated with %D90. Patients whose treatment was planned preoperatively experienced a median increase of 18.4% in target volume. A negative correlation between the amount of edema and the %D90 was found to be statistically significant (-0.55, P = 0.0047). All patients who underwent prostate brachytherapy experienced intraoperative prostatic edema. When planned intraoperatively, the amount of edema had no impact on the %D90. This may be because of the ability of intraoperative computer-optimized treatment planning to account for edema related to the procedure. Preplanned patients who encountered a greater degree of intraoperative edema had less %D90 target coverage.

OBJECTIVE:To determine the impact of clinical nodal stage on distant metastasis (DM) in patients with squamous cell carcinoma of the larynx (SCCL). METHODS:Six hundred sixty-two previously untreated SCCL patients treated at a tertiary care cancer center from January 1984 to December 1998 were eligible for analysis. The end point of interest was development of DM following treatment. Distant metastasis-free survival (DMFS) was calculated by the Kaplan-Meier method; predictors of outcome were identified by univariate and multivariate analysis. The primary tumor site was glottic in 55%, supraglottic in 40%, and trans/sub glottic in 5%; 40% had locoregionally advanced (stage III/IV) tumors. At initial presentation, 25% of patients (12% N1, 11% N2, and 2% N3) had clinically metastatic nodes. RESULTS:DM were recorded in 67 patients (10%; lung, 45%; soft tissue, 13%; bone, 10%; multiple sites, 28%). The median time to DM was 18 months (range, 1-109). With a median follow-up of 60 months, the 5-year DMFS was 88%. Even after accounting for the type of index treatment, the only significant predictor of worse DMFS on multivariate analysis was a higher clinical N stage (P < 0.0001). The relative risk for DM was 0.5 (95% CI, 0.2-1.4; P = NS) for cN1, 3.2 (95% CI, 1.7-5.9; P < 0.0001) for cN2, and 7.5 (95% CI, 3.1-17.9; P < 0.0001) for cN3 disease compared with clinically N0 patients. CONCLUSION/CONCLUSIONS:Regardless of the index treatment modality, primary tumor site, or T stage, a higher clinical N stage at the time of presentation independently and significantly increases the risk of DM in patients with SCCL.

PURPOSE: Treatment of extremity sarcomas occasionally requires tissue transfer in the form of pedicle flaps, free flaps, or skin grafts to repair surgical defects. These tissues are often subject to radiation (RT) and are therefore at risk for wound breakdown requiring reoperation. This study reviews a single center's experience with tissue transfer and postoperative RT. METODS AND MATERIALS: Between 1983 and 2000, 43 adult patients (>16 years old) with primary high-grade soft tissue extremity sarcomas underwent limb-sparing surgery and reconstruction of their surgical defects, followed by adjuvant RT. The reconstructions were as follows: pedicle flaps (n = 14), free flaps (n = 10), skin grafts (n = 4), or a combination (n = 15). Postoperative external beam radiation therapy (EBRT) (median dose: 63 Gy) alone was given to 27 patients (63%). Adjuvant brachytherapy (BRT) was given to 16 patients (37%); BRT alone (median dose: 45 Gy) was given to 12 patients and combined with EBRT for 4 patients (EBRT: 45 Gy; BRT: 20 Gy). Comorbid conditions such as diabetes, hypertension, tobacco use, and obesity (calculated using body mass index >or=30) were present in 30 patients (70%). Tumor characteristics were as follows: 26 were >5 cm in size, 37 were deep, and 30 were in the lower extremity. The median follow-up time, calculated from the date of operation, was 32 months. Five of 43 patients suffered wound complications necessitating reoperation; however, 3 patients developed complications before initiation of RT and were therefore excluded from the analysis. Two of 43 patients (5%) required reoperation for wound complications after RT; 1 of these patients ultimately required amputation for necrosis. The 5-year overall wound reoperation rate was 6% (95% confidence interval: 0-14%). The influence of patient and tumor characteristics, as well as the type of RT, on the wound reoperation rates is as follows: BRT vs. EBRT (17% vs. 0%, p = 0.06); upper vs. lower extremity (0% vs. 8%, p = 0.41); 5 cm (8% vs. 4%, p = 0.9); comorbidity vs. no comorbidity (3% vs. 13%, p = 0.8); age 50 (8% vs. 4%, p = 0.8). CONCLUSION: Based on this review, most tissue transfers (95%) tolerated subsequent adjuvant radiation therapy well. Although more wound complications necessitating reoperation were seen in patients who received BRT, whether this is because of the inherent susceptibility of flaps and skin grafts to breakdown in the immediate postoperative period vs. the direct result of BRT needs further investigation.

PURPOSE/OBJECTIVE:We have developed an intraoperative three-dimensional (3D) conformal treatment planning system for permanent prostate implantation in an effort to reduce toxicity further and improve the accuracy of this procedure. We report the preliminary outcome of patients with localized prostate cancer treated with this approach. METHODS AND MATERIALS/METHODS:Two hundred forty-eight patients with clinically localized prostate cancer were treated with transperineal ultrasound-guided permanent prostate implantation using a real-time intraoperative 3D conformal technique (I-3D) between 1997 and 2001. A genetic algorithm optimization program intraoperatively evaluated the dose deposited throughout the entire 3D volume for multiple seed configurations to identify which seed-loading pattern adhered best to the predetermined target, urethral and rectal dose constraints. The median follow-up time in these patients was 27 months (range 12-51). The dosimetric outcome and acute toxicity profile of these 248 patients were compared with those of patients who were treated between 1988 and 1996 at our institution with a preplanned transperineal implantation technique (PP). RESULTS:Postimplantation dosimetric analysis of the I-3D group demonstrated that the median value of the percentage of the target volume treated to at least the prescription dose (V(100)) was 96%, and the target coverage with the prescription dose (PD) was </=90% in only 3% of these patients. In contrast, among patients treated with the PP method, the median V(100) was 88% and the target coverage with the PD was </=90% in 60% of these patients (p < 0.001). For the I-3D patients, the median and maximal dose to the urethra was 140% and 170% of the PD, respectively, compared with 263% and 532%, respectively, for patients treated with the PP technique. The percentage of urinary symptom resolution at 6, 12, 18, and 24 months for the I-3D cohort was 39%, 72%, 90%, and 97%, respectively. In contrast, the percentage of symptom resolution at the same intervals for patients treated with the PP technique was 12%, 20%, 31%, and 42% (p < 0.001). Multivariate analysis demonstrated that the I-3D technique was an independent predictor of improved target coverage, reduced urethral dose, and more rapid resolution of urinary-related symptoms. The improved dosimetric conformity with the I-3D technique did not compromise the biochemical outcome, as the 4-year actuarial prostate-specific antigen relapse-free survival rate for this group was 97%. CONCLUSION/CONCLUSIONS:The integration of an intraoperative optimization program with 3D dose evaluation throughout the target volume for prostate brachytherapy has consistently achieved excellent target coverage with the PD, and the dose levels to normal tissues were effectively restricted to tolerance ranges. These changes have led to a more favorable acute toxicity profile for patients treated with this technique without compromising biochemical control.

PURPOSE: Delivering high dose to prostate with external beam radiation has been shown to improve local tumor control. However, it has to be carefully performed to avoid partial target miss and delivering excessive dose to surrounding normal tissues. One way to achieve safe dose escalation is to precisely localize prostate immediately before daily treatment. Therefore, the radiation can be accurately delivered to the target. Once the prostate position is determined with high confidence, planning target volume (PTV) safety margin might be reduced for further reduction of rectal toxicity. A rapid computed tomography (CT)-based online prostate localization method is presented for this purpose. METHODS AND MATERIALS: Immediately before each treatment session, the patient is immobilized and undergoes a CT scan in the treatment position using a CT scanner situated in the treatment room. At the CT console, posterior, anterior, left, and right extents of the prostate are manually identified on each axial slice. The translational prostate displacements relative to the planned position are estimated by simultaneously fitting these identified extents from this CT scan to a template created from the finely sliced planning CT scan. A total of 106 serial CT scans from 8 prostate cancer patients were performed immediately before treatments and used to retrospectively evaluate the precision of this daily prostate targeting method. The three-dimensional displacement of the prostate with respect to its planned position was estimated. RESULTS: Five axial slices from each treatment CT scan were sufficient to produce a reliable correction when compared with prostate center of gravity (CoG) displacements calculated from physician-drawn contours. The differences (mean +/- SD) between these two correction schemes in the right-left (R/L), posterior-anterior (P/A), and superior-inferior (S/I) directions are 0.0 +/- 0.4 mm, 0.0 +/- 0.7 mm, and -0.4 +/- 1.9 mm, respectively. With daily CT extent-fitting correction, 97% of the scans showed that the entire posterior prostate gland was covered by PTV given a margin of 6 mm at the rectum-prostate interface and 10 mm elsewhere. In comparison, only 74% and 65% could be achieved by the corrections based on daily and weekly bony matching on portal images, respectively. CONCLUSIONS: Results show that daily CT extent fitting provides a precise correction of prostate position in terms of CoG. Identifying prostate extents on five axial CT slices at the CT console is less time-consuming compared with daily contouring of the prostate on many slices. Taking advantage of the prostate curvature in the longitudinal direction, this method also eliminates the necessity of identifying prostate base and apex. Therefore, it is clinically feasible and should provide an accelerated localization of the prostate immediately before daily treatment

BACKGROUND AND PURPOSE/OBJECTIVE:To assess the effect of internal organ motion on the dose distributions and biological indices for the target and non-target organs for three different conformal prostate treatment techniques. MATERIALS AND METHODS/METHODS:We examined three types of treatment plans in 20 patients: (1) a six field plan, with a prescribed dose of 75.6 Gy; (2) the same six field plan to 72 Gy followed by a boost to 81 Gy; and (3) a five field plan with intensity modulated beams delivering 81 Gy. Treatment plans were designed using an initial CT data set (planning) and applied to three subsequent CT scans (treatment). The treatment CT contours were used to represent patient specific organ displacement; in addition, the dose distribution was convolved with a Gaussian distribution to model random setup error. Dose-volume histograms were calculated using an organ deformation model in which the movement between scans of individual points interior to the organs was tracked and the dose accumulated. The tumor control probability (TCP) for the prostate and proximal half of seminal vesicles (clinical target volume, CTV), normal tissue complication probability (NTCP) for the rectum and the percent volume of bladder wall receiving at least 75 Gy were calculated. RESULTS:The patient averaged increase in the planned TCP between plan types 2 and 1 and types 3 and 1 was 9.8% (range 4.9-12.5%) for both, whereas the corresponding increases in treatment TCP were 9.0% (1.3-16%) and 8.1% (-1.3-13.8%). In all patients, plans 2 and 3 (81 Gy) exhibited equal or higher treatment TCP than plan 1 (75.6 Gy). The maximum treatment NTCP for rectum never exceeded the planning constraint and percent volume of bladder wall receiving at least 75 Gy was similar in the planning and treatment scans for all three plans. CONCLUSION/CONCLUSIONS:For plans that deliver a uniform prescribed dose to the planning target volume (PTV) (plan 1), current margins are adequate. In plans that further escalate the dose to part of the PTV (plans 2 and 3), in a fraction of the cases the CTV dose increase is less than planned, yet in all cases the TCP values are higher relative to the uniform dose PTV (plan 1). Doses to critical organs remain within the planning criteria.