Biomedical subjects

Gary Gustafson

Publications and source records attributed to Gary Gustafson.

13 recordsLinked to original sources

PubMed2006

Hypofractionated conformal HDR brachytherapy in hormone naïve men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups?

PURPOSE: To analyze the long-term effect of local dose escalation using conformal hypofractionated high-dose-rate brachytherapy (HDR-BT) boost and pelvic external-beam radiation therapy (EBRT) in hormone-naïve men with localized prostate cancer. PATIENTS AND METHODS: A total of 579 men were consecutively treated with pelvic EBRT and dose escalating HDR-BT since 1986 in two prospective trials: 378 patients at William Beaumont Hospital (1991-2002), and 201 patients at Kiel University (1986-1999). BT optimization was done modulating both, the dwell times and spatial source positions. A short course of neoadjuvant/concurrent androgen deprivation therapy was given to 222 patients. Hormone-naïve patients only (n = 324) with a follow-up > or = 18 months were analyzed. All patients had at least one poor prognostic factor (stage > or = T2b, Gleason Score > or = 7, pretreatment prostate-specific antigen [PSA] > or = 10 ng/ml): any one factor 122 patients, any two factors 122 patients, and three factors 80 patients. This cohort was stratified by equivalent dose (ED): dose level 1, < or = 94 Gy, n = 58, and dose level 2, > 94 Gy, n = 266, assuming an alpha/beta ratio of 1.2. The ASTRO definition for biochemical failure was used. RESULTS: Mean follow-up was 5.3 years (1.5-13.9 years). For all 324 patients, the 5-year biochemical control (BC) rate was 79%. Cancer-specific survival was 98%, and overall survival 90%. Similar analysis by institution demonstrated no difference in outcomes. For the entire cohort of hormone-naïve men, dose escalation to > 94 Gy resulted in a better 5-year BC of 59% versus 85% (p < 0.001). Discriminating by risk group a striking dose escalation effect was seen in the groups with two or three poor prognostic factors (p = 0.022 and < 0.001, respectively). In the group with only one poor prognostic factor, no statistical difference could be detected questioning the need for ED > 94 Gy. CONCLUSION: The results demonstrate that conformal HDR-BT is a successful method for delivering very high radiation dose to the prostate. The ability to escalate dose to ED > 94 Gy was reflected in improved long-term outcomes in terms of BC, significantly for those patients with two or three poor prognostic factors reaching BC rates of 85%.

Actuarial Analysis↗

PubMed2005

Butenyl-spinosyns, a natural example of genetic engineering of antibiotic biosynthetic genes.

Spinosyns, a novel class of insect active macrolides produced by Saccharopolyspora spinosa, are used for insect control in a number of commercial crops. Recently, a new class of spinosyns was discovered from S. pogona NRRL 30141. The butenyl-spinosyns, also called pogonins, are very similar to spinosyns, differing in the length of the side chain at C-21 and in the variety of novel minor factors. The butenyl-spinosyn biosynthetic genes (bus) were cloned on four cosmids covering a contiguous 110-kb region of the NRRL 30141 chromosome. Their function in butenyl-spinosyn biosynthesis was confirmed by a loss-of-function deletion, and subsequent complementation by cloned genes. The coding sequences of the butenyl-spinosyn biosynthetic genes and the spinosyn biosynthetic genes from S. spinosa were highly conserved. In particular, the PKS-coding genes from S. spinosa and S. pogona have 91-94% nucleic acid identity, with one notable exception. The butenyl-spinosyn gene sequence codes for one additional PKS module, which is responsible for the additional two carbons in the C-21 tail. The DNA sequence of spinosyn genes in this region suggested that the S. spinosa spnA gene could have been the result of an in-frame deletion of the S. pogona busA gene. Therefore, the butenyl-spinosyn genes represent the putative parental gene structure that was naturally engineered by deletion to create the spinosyn genes.

Anti-Bacterial Agents↗

PubMed2005

Lack of benefit from a short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime.

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.

Aged↗

PubMed2005

A dose-escalation trial with the adaptive radiotherapy process as a delivery system in localized prostate cancer: analysis of chronic toxicity.

PURPOSE: To evaluate the validity of the chosen adaptive radiotherapy (ART) dose-volume constraints while testing the hypothesis that toxicity would not be greater at higher tumor dose levels. MATERIALS AND METHODS: In the ART dose escalation/selection trial, treatment was initiated with a generic planning target volume (PTV) formed as a 1-cm expansion of the clinical target volume (CTV). After the first week of therapy, the patient was replanned with a patient-specific PTV, constructed with CT and electronic portal images obtained in the first 4 days of treatment. A new multileaf collimator beam aperture was used. A minimum dose prescribed to the patient-specific PTV, ranging 70.2-79.2 Gy, was determined on the basis of the following rectal and bladder constraints: <5% of the rectal wall has a dose >82 Gy, <30% of the rectal wall has a dose >75.6 Gy, <50% of the bladder volume has a dose >75.6 Gy, and the maximum bladder dose is 85 Gy. A conformal four-field and/or intensity-modulated radiotherapy (IMRT) technique was used. Independent reviewers scored toxicities. The worst toxicity score seen was used as per the Common Toxicity Criteria grade scale (version 2). We divided the patients into three separate groups: 70.2-72 Gy, >72-75.6 Gy, and >75.6-79.2 Gy. Toxicities in each group were quantified and compared by the Pearson chi-squared test to validate our dose escalation/selection model. Grades 0, 1, 2, and 3 were censored as none vs. each category and none vs. any. RESULTS: We analyzed patients with follow-up greater than 1 year. The mean duration of follow-up was 29 months (range, 12-46 months). We report on 280 patients, mean age 72 years (range, 51-87 years). Only 60 patients received adjuvant hormones. Mean pretreatment prostate-specific antigen level was 9.3 ng/mL (range, 0.6-120 ng/mL). Mean Gleason score was 6 (range, 3-9). The lowest dose level was given to 49 patients, the intermediate dose to 131 patients, and 100 patients received the highest dose escalation. One hundred eighty-one patients (65%) were treated to a prostate field only and 99 patients (35%) to prostate and seminal vesicles. Chronic genitourinary and/or gastrointestinal categories were incontinence, persistent urinary retention, increased urinary frequency/urgency, urethral stricture, hematuria, diarrhea, rectal pain, bleeding, ulcer, fistula, incontinence, and proctitis. Toxicity at the high dose level was not different from toxicity at the intermediate or lower dose levels. No significant difference was observed in any of the individual toxicity categories. CONCLUSIONS: By applying the ART process--namely, developing a patient-specific PTV--to prostate cancer patients, significant dose escalation can be achieved without increases in genitourinary or gastrointestinal toxicity. Our data validate the rectal and bladder dose-volume constraints chosen for our three-dimensional conformal and IMRT prostrate radiotherapy planning.

Aged↗

PubMed2005

A new model using number of needles and androgen deprivation to predict chronic urinary toxicity for high or low dose rate prostate brachytherapy.

PURPOSE: Prostate brachytherapy is an established treatment modality in early stage prostate cancer. We retrospectively reviewed our experience with low dose rate (LDR) and high dose rate (HDR) brachytherapy as a single treatment modality for early prostate cancer with emphasis on chronic toxicity. MATERIALS AND METHODS: From June 1996 to August 2003, 253 patients with stage II prostate cancer, prostate specific antigen less than 12 and Gleason score less than 7 were treated with brachytherapy alone at our institution. A total of 92 patients underwent HDR brachytherapy with 192Ir, while 161 underwent LDR brachytherapy with 103Pd. HDR minimum prostate dose was 38 Gy, delivered in 4 fractions with a single implant during 36 hours. For HDR we used real-time dynamic 3-dimensional ultrasound base dosimetry. For 103Pd seed implants the dose was 120 Gy using selective peripheral weighted dose distribution. Treatment was given based on patient preference after pretreatment transrectal ultrasound. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria 2.0. Median followup in all 253 cases was 2.9 years. RESULTS: In all patients the rate of 3-year urinary toxicity grade 2 or greater and grade 3 or greater was 26% and 6.9%, which was not significantly different between HDR and LDR (p = 0.3 and 0.4, respectively). However, grade 1 urogenital toxicity was lower for HDR (p = 0.002). The 3-year grade 2 rectal toxicity rate was 0.8% with no grade 3 or greater events, which was and similar in the HDR and LDR groups (1% and 0.6%, respectively). No cancer related deaths occurred and 4-year overall survival was 99% for HDR and 96.4% for LDR (p = 0.4). The 3-year American Society for Therapeutic Radiology and Oncology biochemical control rate was 90% for LDR and 93% for HDR. Cox multivariate analysis for grade 2 or greater urinary toxicity was significant for the use of 14 or greater needles (HR 6.1, p = 0.02) and hormonal therapy (HR 2.2, p = 0.02). In the absence of risk factors the 4-year grade 2 or greater urinary toxicity rate was 7% vs 65% if the 2 risk factors were present (p <0.001). Impotence crude rates were 18.3% for HDR and 41.3% for LDR (p = 0.002). CONCLUSIONS: HDR and LDR chronic urinary toxicity grade 2 or greater rates were equivalent. However, grade 1 was lower for HDR. The impotence rate was decrease by half with HDR. Neoadjuvant hormonal therapy and 14 or greater needles were significantly associated with increased chronic urinary toxicity on multivariate analysis.

Aged↗

PubMed2004

Long-term outcome by risk factors using conformal high-dose-rate brachytherapy (HDR-BT) boost with or without neoadjuvant androgen suppression for localized prostate cancer.

PURPOSE: The aim of this study is to analyze, during the prostate-specific antigen (PSA) era, the long-term outcome of patients treated with conformal high-dose-rate (HDR) brachytherapy boost to the prostate with or without androgen deprivation therapy (ADT) when patients are stratified by risk factors for failure. METHODS AND MATERIALS: Between 1986 and 2000, 611 patients were treated for clinically localized prostate cancer in three prospective trials of external beam radiation therapy (EBRT) and dose-escalating HDR brachytherapy (BT) boost. There were 104 patients treated at Seattle, 198 at Kiel University, and 309 at William Beaumont Hospital. Of the 611 patients, 177 received a short course of neoadjuvant/concurrent ADT. The patients were divided into three risk groups. Group I, comprised of 46 patients, had stage < or =T2a, Gleason score (GS) < or = 6, and initial PSA (iPSA) < or = 10 ng/mL. Group II comprised 188 patients with stage > or =T2b, GS > or = 7, and iPSA > or = 10, with any one factor higher. Group III included 359 patients with any two risk factors higher. The American Society for Therapeutic Radiology and Oncology definition for biochemical failure was used. RESULTS: The mean follow-up was 5 years (range, 0.2-15.3). For the 611 patients, the 5-year and 10-year biochemical control (BC) rates were 77% and 73%, disease-free survival (DFS) was 67% and 49%, and cause-specific survival (CSS) was 96% and 92%, respectively. BC at 5 years for Group I patients was 96%, for Group II 88%, and for Group III patients 69%. CSS at 5 years was 100% in Group I, 99% in Group II, and 95% in Group III patients. In univariate and multiple regression analyses for BC, risk group, stage, iPSA, and GS were significant in predicting failure. However, age, follow-up interval, and ADT did not. CONCLUSIONS: EBRT with HDR-BT produced excellent long-term outcomes in terms of BC, DFS, and CSS in patients with prostate cancer even for those at highest risk. Conformal HDR-BT is both a precise dose delivery system and an effective treatment for both favorable and unfavorable prostate cancer. The addition of a short course of neoadjuvant/concurrent ADT failed to improve outcome. The results were similar at all three institutions, giving credence to the reproducibility of the brachytherapy treatment.

Aged↗

PubMed2004

Partial breast irradiation in breast conserving therapy by way of intersitial brachytherapy.

OBJECTIVE: To examine early and late toxicities, evaluate cosmetic results, and determine the need for reoperation or additional diagnostic procedures in patients treated with accelerated partial breast irradiation (APBI) delivered by way of an interstitial implant in breast-conserving therapy. METHODS: A total of 199 patients with stage I or II breast cancer were managed with lumpectomy followed by radiation restricted to the tumor bed using an interstitial implant (APBI). Retrospective analyses were performed for early and late toxicities (infection, fat necrosis, breast pain, edema, erythema, fibrosis, pigmentation changes, and telangiectasias), need for reoperation or additional diagnostic procedures, cosmetic results, and local control. Patient selection criteria by the surgeon for referral to RT for APBI included age, tumor size, histology, nodal status, margin status, and absence of extensive intraductal component. Treatment was delivered with either a low-dose or high-dose rate implant. Median follow-up was 5.7 years, and 54% of the patients were followed-up for >7 years. RESULTS: Infections developed in 22 of 199 (11%) patients: 7% early (</=1 month after implant removal) and 4% late (>1 month after implant removal). Five of the 22 patients (2% of all patients) required operative intervention for the infection, either incision and drainage or debridement. There was a statistically significant difference between infection rates with open (8.5%) versus closed (2.5%) cavity placement of the interstitial needles (P = 0.005). There was no statistically significant difference between low-dose rate (inpatient) and high-dose rate (outpatient) treatment (P = 0.207). Forty-five patients (23%) had an additional diagnostic procedure to evaluate a suspicious or uncertain finding on physical examination or mammogram. Fibrosis and fat necrosis were found in 26 of the 45 patients. The incidence of fat necrosis increased with time. More patients were found to have fat necrosis after 5 years. One patient had fat necrosis diagnosed at <6 months; 8 patients (4% of total) at >/=6 months to <2 years; 10 patients (5% of total) at >/=2 years to <5 years; and 22 patients (11% of total) at >/=5 years. The majority of fat necrosis was detected on mammogram (80%) and was asymptomatic (78%). Cosmesis and toxicities were assessed at 3 defined time points: </=6 months, 2 years, and >/=5 years of follow-up. Using Harvard criteria, good to excellent cosmetic results were observed in >90% of patients. Breast pain, edema, and erythema diminished with time. Of the 199 cases, there were only 5 ipsilateral breast failures, yielding a 5-year actuarial local recurrence rate of 1.2%. Of these 5 failures, 2 were true recurrences/marginal misses, yielding a 5-year actuarial true recurrence/marginal miss rate of 0.5%. The 5-year actuarial cause-specific survival rate was 99% for APBI patients. CONCLUSIONS: In selected patients with early-stage breast cancer, APBI with targeted interstitial brachytherapy offers 5-year results comparable with conventional breast-conserving therapy employing whole-breast radiation therapy. Minimal long-term toxicities were noted, most of which demonstrated continued resolution over time. Acceptable acute (7%) and delayed (4%) infection rates were observed. Fat necrosis was identified with increasing frequency with time, but the majority was asymptomatic. Cosmetic results are good to excellent (>90%). Continued follow-up by the surgeon will be required to determine the long-term efficacy of this alternative treatment approach.

Adult↗

PubMed2003

High dose rate brachytherapy in the treatment of prostate cancer.

The optimal treatment of patients with localized prostate cancer remains controversial. Significant clinical data are available, however, demonstrating that patients treated with radiation therapy (RT) have a significantly better outcome as the dose to the gland is increased. What remains debatable, however, is how to best deliver these higher doses of RT without significantly increasing normal tissue toxicities. Conformal high dose rate brachytherapy (C-HDR BT) represents an alternative means of precise dose delivery that offers similar tumoricidal effects as three-dimensional (3D) conformal external beam radiotherapy (EBRT) or permanent interstitial prostate seed implants with potential additional advantages. Since C-HDR BT consists of temporarily placing afterloading needles or catheters directly into the prostate gland under real-time ultrasound guidance, a steep dose gradient between the prostate and adjacent normal tissues can be generated that is minimally affected by organ motion and edema or treatment setup uncertainties. The ability to control the amount of time the single HDR radioactive source "dwells" at each position along the length of each brachytherapy catheter further enhances the conformity of the dose. In addition, recent radiobiological data on prostate cancer treatment suggest that C-HDR BT should produce tumor control and late normal tissue side effects that are at least as good as achieved with conventional fractionation, with the additional possibility that acute side effects might be reduced. Published data from several groups performing C-HDR BT as boosts in patients with locally advanced disease have supported these assumptions. Combined with the physical advantages discussed above, C-HDR BT should provide similar tumor control as 3D conformal EBRT with the added advantages of reduced treatment times, less acute toxicity, and no additional technological requirements to account and correct for treatment setup uncertainties and organ motion. Due to the success of C-HDR BT as boost treatment in locally advanced disease, this form of radiation treatment has recently been applied to low-risk prostate cancer patients as an alternative brachytherapy technique to permanent interstitial seed implantation. Advantages in this setting include an improved ability to define and deliver the prescribed dose, a significantly shortened treatment schedule compared to 3D conformal EBRT, and the fact that patients are not radioactive after implantation.

Brachytherapy↗

PubMed2003

Inter-society standards for the performance of brachytherapy: a joint report from ABS, ACMP and ACRO.

PURPOSE: The proliferation of various brachytherapy modalities for different anatomical sites necessitates the creation of standards for brachytherapy. METHODS: A panel consisting of members of The American Brachytherapy Society (ABS), The American College of Medical Physics (ACMP) and The American College of Radiation Oncology (ACRO) developed standards for the clinical practice and quality assurance (QA) of brachytherapy. These were based upon their clinical experience and a review of the literature. RESULTS: Recommended practice standards are presented for clinical processes, treatment planning, equipment, facilities, QA, dose evaluation, dose specification, dose reporting, the training, and credentialing of personnel, and radiation control/safety/protection. Safe and efficacious performance of brachytherapy requires a highly structured QA program and carefully designed treatment delivery processes, as well as a coordinated effort amongst the team members. CONCLUSION: Standards for clinical brachytherapy are proposed. Practitioners are encouraged to use these standards to design and implement a consistent and efficacious brachytherapy program.

Brachytherapy↗

PubMed2003

Conformal high dose rate brachytherapy improves biochemical control and cause specific survival in patients with prostate cancer and poor prognostic factors.

PURPOSE: To improve outcome for patients with prostate cancer with poor prognostic factors higher than conventional radiation doses are required. To achieve this outcome a brachytherapy boost was given. We report the results of the first high dose rate dose-escalation brachytherapy trial. MATERIALS AND METHODS: Between 1991 and 2000, 207 patients were prospectively enrolled in a dose escalation trial including pelvic radiotherapy and conformal high dose rate prostate brachytherapy boost. The dose was increased from 5.5 to 11.5 Gy. per implant. Patient eligibility for the study included pretreatment prostate specific antigen 10 or greater, Gleason 7 or greater or clinical stage T2b or higher. No patient received hormonal therapy. The American Society for Therapeutic Radiology and Oncology consensus panel definition of biochemical failure was applied. RESULTS: Median patient age was 69 years. Mean followup was 4.7 years (range 0.6 to 10.4). The 5-year actuarial biochemical control rate was 74%. The 5-year biochemical control was 85% for 1 poor prognostic factor, 75% for 2 and 50% for all 3 (p = 0.001). On Cox regression multivariate analysis lower brachytherapy dose, and higher Gleason and nadir value were associated with biochemical failure. The 5-year actuarial overall survival was 92%, cause specific survival 98% and disease-free survival 68%. The 5-year actuarial rates of complications were 8% and 0% for grades 3 and 4 genitourinary, and 0.5% and 0.5% for grades 3 and 4 gastrointestinal, respectively. The 5-year actuarial impotence rate was 51%. CONCLUSIONS: For patients with poor prognostic factors external beam radiation therapy with conformal high dose rate brachytherapy boost improved biochemical control, resulting in a high cause specific survival rate with low toxicity. Another important advantage is that the patient is not radioactive after the high dose rate implant.

Actuarial Analysis↗

PubMed2003

No apparent benefit at 5 years from a course of neoadjuvant/concurrent androgen deprivation for patients with prostate cancer treated with a high total radiation dose.

PURPOSE: We examined the survival impact of a course of 6 months or less of adjuvant/concurrent androgen deprivation in patients with unfavorable prostate cancer treated to high radiation doses with external beam (EBRT) and a high dose rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Between 1986 and 2000, 507 patients were treated with pelvic EBRT (46 Gy) with HDR prostate brachytherapy as a boost. The biological equivalent EBRT dose was between 90 and 130 Gy. At Kiel University and at William Beaumont Hospital 198 and 309 patients were treated. Patient eligibility was pretreatment prostate specific antigen 10 ng/ml or greater, Gleason score 7 or greater, or clinical stage T2b or greater. The brachytherapy dose was escalated from 5.5 x 3 to 15 x 2 Gy. Patients were divided between 177 receiving and 330 not receiving androgen suppression therapy (AST). AST was given for a mean of 6 months. The American Society for Therapeutic Radiology and Oncology biochemical failure definition was used. RESULTS: Mean patient age was 68 years. Mean followup was 4.8 years (range 0.7 to 15.3), that is 4.5 years for AST and 4.9 for radiation alone. Five-year actuarial rates for biochemical control were 74% and 76%, for overall survival they were 81% and 87%, and for disease-free survival they were 67% and 66%, while cause specific survival with and without AST was 90% and 98%, and the 5-year metastatic rates were 10.7% and 6.9%, respectively. On multivariate analysis AST did not improve biochemical control. CONCLUSIONS: Pelvic EBRT interdigitated with a transrectal ultrasound guided HDR boost is an excellent method of delivering a high radiation dose to the prostate without rendering the patient radioactive. This trial showed high overall, cause specific and no biochemical evidence of disease survival. For this unfavorable group of patients the addition of a course of 6 months or less of neoadjuvant/concurrent AST to a high radiation dose did not appear to confer a 5-year therapeutic advantage. However, it added side effects and the significant cost of hormones.

Actuarial Analysis↗

PubMed2002

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

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.

Aged↗

PubMed2002

Financial standards for HMOs.

In today's health care environment, it is important to assess the liquidity and profitability performance of HMOs. This study focuses on three liquidity ratios and three profitability ratios derived from national databases of between 740 and 776 HMOs from 1996 to 1999. Most of the HMOs appear to be using more debt and are less liquid now than they were in 1995. Since administrative overhead costs and dollars spent on medical costs have been increasing, HMOs' margins have been consistently negative. A more careful analysis of overhead costs and the cost of the delivery of medical services could result in improved HMO quality of care, efficiencies, and a return to positive profit margins.

Accounts Payable and Receivable↗