Faculty Bibliography

PURPOSE/OBJECTIVE:Although permanent seed prostate brachytherapy is associated with a low risk of serious morbidity, proctitis and prolonged irritative and obstructive urinary symptoms may occur. Data are accumulating to help establish thresholds or guidelines for minimizing toxicity, however, no uniform method of defining and calculating the dose to critical organs currently exists. We set out to examine the existing data and propose a uniform method of reporting such that results from different centers can more easily be compared. METHODS AND MATERIALS/METHODS:In preparation for a panel discussion at the American Brachytherapy Society 2004 Annual Meeting, four members with expertise in prostate dosimetry and critical organ assessment performed a literature search and, supplemented with their clinical experience, formulated a proposal for defining and reporting dose in a standardized fashion to the critical organs for permanent seed prostate brachytherapy. RESULTS:As previously recommended by the American Brachytherapy Society, postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy. The standard imaging for postplan assessment is the CT scan. The interval between seed implantation and postplan assessment should be reported. For rectal and urinary morbidities, the critical organs are considered to be the anterior rectum and the prostatic urethra, respectively. For erectile dysfunction, both the neurovascular bundle and penile bulb have been implicated. The rectum should be contoured on all CT scan slices where radioactive seeds are visible. Both the inner and outer walls should be contoured. The dose should be reported as RV100 and RV150, the volumes in cubic centimeters of the rectal wall receiving 100% and 150% of the prescribed dose, respectively. The urethra should be contoured as a structure on each slice where seeds can be seen. The urethra should be identified by either catheterization or fusion with transrectal ultrasound. The dose should be reported as UrD5 and UrD30, which are, respectively, the dose to 5% and 30% of the urethra in Gray. As well, a UrV150 should be reported, which is the volume in cubic centimeters of the urethra receiving 150% of the prescribed dose. No recommendations can be made at this time for reporting neurovascular bundle or penile bulb doses. CONCLUSIONS:It is essential that toxicity data be collected and reported in a uniform fashion. Thus, the critical organs for toxicity must be defined and the corresponding dosimetry reported in a standard fashion such that guidelines can be established in the future based on data from a cross-section of centers.

PURPOSE/OBJECTIVE:To report results of a phase II trial of high-dose-rate intra-operative radiation therapy (HDR-IORT) for malignant pleural mesothelioma (MPM). METHODS AND MATERIALS/METHODS:Seven patients had extrapleural pneumonectomy with IORT (EPP/IORT) and 6 patients had pleurectomy/decortication with IORT (PD/IORT) between 1994 and 1996. IORT was delivered with 192Ir using a customized applicator with a remote afterloader. A median of 3 sites were treated to a median area of 143 cm2. A dose of 1500 cGy was prescribed at each site, with 1000 cGy delivered to the mediastinum. Postoperative external beam radiation therapy (EBRT) was given 3-5 weeks later. Median follow-up was 8 months (range, 1-84 months). RESULTS:Five patients developed local failure. Two-year local control and survival rates were 35% and 23%, respectively. Mortality was 2/13 (15%), 1 from each surgical group. Serious complications requiring further intervention occurred in 3/6 (50%) of the EPP/IORT group and 1/5 (20%) of the PD/IORT group. CONCLUSIONS:HDR-IORT after EPP for MPM is prohibitively toxic and has been abandoned, while its use with PD remains in question.

PURPOSE/OBJECTIVE:To report changing trends in external beam radiotherapy (EBRT) delivery practice for clinically localized prostate cancer as determined from the 1999 survey from the American College of Radiology National Patterns of Care Study. METHODS AND MATERIALS/METHODS:The 1999 survey included a weighted sample of 36,496 patient records obtained from a stratified two-stage sample of 554 patient records. Patients were surveyed from 58 institutions and were treated between January 1999 and December 1999. Of these, 36% (weighted sample size, 13,293; unweighted sample size, 162) were treated with brachytherapy with or without EBRT and 64% (weighted sample size, 23,203; unweighted sample size, 392) were treated with EBRT only. The latter group is the subject of this report. The following trends in clinical practice were analyzed according to prognostic risk groups and other variables and compared with the results of the prior surveys: use of androgen deprivation therapy (ADT) in combination with EBRT, higher prescription dose levels, and administration of elective whole pelvic RT (WPRT). RESULTS:The incidence of ADT use for favorable, intermediate, and unfavorable-risk groups was 31%, 54%, and 79%, respectively. A multivariate logistic regression analysis revealed a statistically significantly increased likelihood of intermediate (p = 0.001) and unfavorable (p <0.0001) risk groups treated with ADT in conjunction with EBRT compared with favorable-risk patients. ADT use was more prevalent among treated patients in the 1999 survey than in the 1994 survey (51% vs. 8%, p <0.0001). Compared with the prior survey, a greater percentage of patients were treated with higher radiation doses in the 1999 survey (> or =72 Gy, 45% in 1999 vs. 3% in 1994, p <0.0001). In the 1999 survey, the proportion of patients with favorable, intermediate, and unfavorable tumors treated to doses > or =72 Gy was 43%, 38%, and 60%, respectively, compared with 4%, 3%, and 1%, respectively, in the 1994 survey. Compared with the 1994 survey, a large increase in the number of patients treated with brachytherapy (36% vs. 3%, p <0.0001). The frequency of WPRT use decreased from 92% in 1989 to 52% in 1994 to 23% in 1999. For the 1999 survey, a multivariate analysis indicated that unfavorable-risk patients (p = 0.016) and intermediate-risk patients (p = 0.018) were more likely to be treated with WPRT compared with favorable-risk patients. Nevertheless, even among unfavorable-risk patients, a substantial decline had occurred in the use of WPRT for the 1999 survey (70% for the 1994 survey compared with the 31% for the current survey; p = 0.003). CONCLUSION/CONCLUSIONS:The significantly increased use of ADT for high-risk patients and higher radiation doses, especially for intermediate- and high-risk patients, reflects the penetration and growing acceptance of clinical trial results that have demonstrated the efficacy of these treatment approaches. The relatively high proportion of favorable-risk patients treated with high radiation dose levels was greater than expected. A large increase in brachytherapy was observed compared with prior surveys. Most treated patients with high-risk disease did not undergo elective WPRT, which likely reflects the influences of prior trials, stage migration, and the commonly held belief that WPRT provides minimal benefit in the setting of higher radiation doses.

OBJECTIVES/OBJECTIVE:To describe the 5-year outcomes of patients with high-risk localized prostate cancer treated with neoadjuvant estramustine and vinblastine followed by concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). METHODS:A total of 23 patients completed therapy consisting of two 8-week cycles of vinblastine, weekly as 4 mg/m2, followed by 8 weeks of concomitant chemotherapy and 3D-CRT. Estramustine was given daily at 10 mg/kg in three divided doses. 3D-CRT consisted of a total dose of 7560 cGy. RESULTS:Assessable patients include 9 with Stage T3 or greater tumors and 5 with lymph node metastasis at diagnosis. All patients had a Gleason score 7 or greater. The median follow-up was 60 months. Of the 23 assessable patients, 15 (65%) experienced biochemical relapse by American Society for Therapeutic Radiology Oncology criteria. The median time to prostate-specific antigen relapse was 12 months (range 7 to 16). Five patients (22%) developed metastases. The median time to metastasis had not been reached by last follow-up. Of the 23 assessable patients, 11 (48%) received no additional therapy and had noncastrate testosterone levels. Six patients had no evidence of disease and 9 patients were receiving androgen blockade. Three patients died (one of prostate cancer and two of other diseases). CONCLUSIONS:A substantial proportion of patients with unfavorable-risk localized prostate cancer achieved long-term disease control with estramustine and vinblastine and concurrent 3D-CRT, no significant long-term toxicities were seen and 48% underwent no further therapy after RT. These long-term findings support the continued study of chemotherapy combined with RT as a potential alternative to prolonged androgen deprivation.

Because innovations in radiation treatment planning have dramatically improved the precision of external beam radiotherapy for prostate cancer with the advent of conformal three-dimensional conformal therapy and intensity modulated radiotherapy, similar developments are emerging for prostate brachytherapy. Computer software programs are facilitating the ability to rapidly create conformal treatment plans in the operating room, taking into account the three-dimensional reconstruction of the prostate target and adhering to dose-volume constraints of the normal tissues including the urethra and rectum. Although excellent dose distributions can be achieved with pre-planning techniques, intraoperative planning takes into account the intraoperative geometry of the prostate and the surrounding normal tissues and can consistently produce seed implants with reduced urethral and rectal doses while delivering the intended prescription dose to the target volume. Current developments are pursuing methods to dynamically modify the treatment plan as the implant procedure is ongoing based on the coordinates of the deposited seeds. Such approaches will minimize the possibility of tumor underdosage and further enhance the conformality of prostate brachytherapy.

CONTEXT/BACKGROUND:Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. OBJECTIVE:To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. DESIGN, SETTING, AND PATIENTS/METHODS:Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. MAIN OUTCOME MEASURE/METHODS:Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. RESULTS:Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. CONCLUSIONS:Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.