Conformal High Dose Rate Brachytherapy Research Articles

Prostate cancer considered low or intermediate risk for biochemical failure according to the rtog-astro phoenix definition: Results of the use of neoadjuvant androgen deprivation before high-dose rate brachytherapy and external beam radiotherapy

16121 Background: Patients treated with radiation therapy have a significantly better outcome as the dose to the prostate is increased. Conformal high dose rate brachytherapy (HDR) is a successful method for delivering higher dose of radiation. This is a retrospective analysis of patients presenting with low (LR) or intermediate (IR) risk features, who were submitted or not to neoadjuvant androgen deprivation (NAAD). Methods: Charts of patients treated with HDR and localized 3DRT between 1997 and 2005 were reviewed. At the discretion of the referral urologist patients had NAAD (goserelin +/− flutamide or ciproteron acetate). 3 to 6 months. Results: 142 patients were eligible for study entry, 84 (59.1%) had no NAAD. Median age of the patients was 70 years (range, 53–81 years). Median follow-up was 6 years. There were 77 (54.2%) of patients into the LRG and 65 (45.8%) into IRG. The dose of EBRT ranged from 40 to 54 Gy (median 47 Gy). The HDR dose ranged from 16 to 24 Gy given in 4 fractions, BID, in two days. Median HDR dose was 20 Gy. Of the patients who had NAAD, 38 (26.8%) of the patients had central or total androgen blockage and 20 (14.1%) patients had peripheral blockage only. The crude overall survival (OS) rate at 4-year was 95.1%. The 5- and 10-year actuarial OS rates were 93.6% and 85.8%, respectively. The crude biochemical control (BC) rate at 4-year was 79.2%. Actuarial BC rates at 5- and 10-year were 91.4% and 59.6% for LRG and for IRG were 89.2% and 45.4%, respectively (p=0.308). NAAD did not influence the BC rates (p=0.477). Conclusion: dose of radiation prescribed seems to be an important factor related to BC. So far in our own experience, HDR and 3DRT are successful forms of treatment combination, but data from prospective randomized trials are still missing. We favour the use of adjuvant androgen deprivation over NAAD for patients presenting with adverse prognostic factors. No significant financial relationships to disclose.

High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer

We report the outcome and toxicities of high dose rate brachytherapy as a boost for localized prostate cancer. Between 1996 and 2003, 309 patients with prostate carcinoma were treated with external beam radiation therapy and high dose rate brachytherapy. Furthermore, 36% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 3 groups. Group 1 of 67 patients had Gleason score 6 or less, pretreatment prostate specific antigen 10 ng/ml or less and clinical stage T2a or less. Group 2 of 109 patients had Gleason score 7 or greater, pretreatment prostate specific antigen greater than 10 ng/ml and clinical stage T2b or greater. Group 3 of 133 patients had 2 or more of these higher risk factors. At a median followup of 59 months the 5-year biochemical control rate, as defined by the American Society for Therapeutic Radiation and Oncology, was 86%, cause specific survival was 98% and overall survival was 91%. Biochemical control in stratified groups 1 to 3 was 98%, 90% and 78%, respectively. On univariate analysis risk group, pretreatment prostate specific antigen and Gleason score were significant predictors of biochemical control. However, on multivariate analysis only risk group and pretreatment prostate specific antigen were significant. Using the Common Toxicity Criteria scale there were 2 cases of grade 3 acute urinary toxicity. Regarding late side effects 4% of patients had grade 3 genitourinary toxicity and 1 had a grade 4 rectal complication. External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent biochemical control, cause specific survival and overall survival with minimal severe acute or late complications.

High Dose Rate Iridium-192 Brachytherapy as a Component of Radical Radiotherapy for the Treatment of Localised Prostate Cancer

Aims To assess the treatment outcomes and toxicity of conformal high dose rate (HDR) brachytherapy boost as a means of radiation dose escalation in patients with localised prostate cancer. Materials and methods Between December 1998 and July 2004, 65 consecutive patients with localised prostate cancer (magnetic resonance imaging-staged T1–3 N0 M0) were treated with external beam radiation therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The patients selected this treatment modality in preference to entering an ongoing randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA) and Gleason score were included. The primary end point was biochemical disease-free progression. Late treatment-related morbidity was graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria. Results The median patient age was 67.3 years (range 47.9–80). Sixty patients (92.3%) had intermediate- to high-risk disease defined by clinical stage, presenting PSA and Gleason score/World Health Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6–5.8), two patients had died of metastatic disease and another four patients had PSA relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%. Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal toxicities were observed. Conclusions These results suggest that the combined modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality with acceptable acute and late toxicities, comparable with those of EBRT alone. It offers an attractive conformal treatment modality with the potential of further dose escalation in the treatment of localised prostate cancer.

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer

Purpose: To evaluate treatment outcome of 3D conformal high dose rate (HDR) brachytherapy and external beam irradiation (EBRT) combined with temporary androgen deprivation for patients with localized prostate cancer. Patients and methods: Between January 1997 and September 1999 we treated 102 patients with stage T1–3 N0 M0 prostate cancer. Stage T1–2 was found in 71, T3 in 31 patients. Median pretreatment PSA level was 15.3 ng/ml. After ultrasound-guided transrectal implantation of four afterloading needles, CT based 3D brachytherapy planning was performed. All patients received four HDR implants using a reference dose per implant of 5 or 7 Gy. Time between each implant was 14 days. After brachytherapy EBRT followed up to 39.6 or 45.0 Gy. All patients received temporary androgen deprivation, starting 2–19 months before brachytherapy, ending 3 months after EBRT. Results: Median follow-up was 2.6 years (range 2.0–4.1 years). Actuarial biochemical control rate was 87% at 2 years and 82% at 3 years. In 14 patients we noted biochemical failure, in five patients clinical failure. Overall survival was 90%, disease specific survival 98.0% at 3 years. Acute grade 3 toxicity occurred in 4%, late grade 3 toxicity in 5%. One patient developed a prostatourethral-rectal fistula as late grade 4 toxicity. The conformal quality of 300 HDR implants was analyzed using dose volume histograms. Conclusions: 3D conformal HDR brachytherapy and EBRT combined with temporary androgen deprivation is an effective treatment modality for prostate cancer with minimal associated toxicity and encouraging biochemical control rates after a median follow-up of 2.6 years.

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 ≤T2a, Gleason score (GS) ≤ 6, and initial PSA (iPSA) ≤ 10 ng/mL. Group II comprised 188 patients with stage ≥T2b, GS ≥ 7, and iPSA ≥ 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.

Benefit from prostatic local dose escalation using conformal high dose rate brachytherapy (HDR-BT) in hormone naive men with localized prostate cancer

Purpose/Objective: To analyze the effect of local prostatic dose escalation using conformal HDR-BT in hormone naive men treated with pelvic external beam radiation therapy (EBRT) for localized prostate cancer.

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.

18 oral Long-term outcome in 330 hormone naive men with localized prostate cancer following local dose escalation using conformal High Dose Rate brachytherapy (HDR-BT)

18 oral Long-term outcome in 330 hormone naive men with localized prostate cancer following local dose escalation using conformal High Dose Rate brachytherapy (HDR-BT)

The role of high-dose rate brachytherapy in locally advanced prostate cancer

Although the optimal management of patients with locally advanced prostate cancer remains undefined, sufficient clinical data have emerged showing that patients treated with radiation therapy (RT) have a significantly better outcome as the dose to the gland is escalated. What remains unresolved, however, is how to best deliver these higher tumoricidal doses of RT. Conformal high-dose rate brachytherapy (C-HDR BT) is an alternative means of precise dose escalation that offers similar tumoricidal effects as 3-dimensional (3D) conformal external beam radiotherapy (EBRT) with potential additional advantages. By placing HDR afterloading needles 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 unaffected by organ motion and edema or treatment setup uncertainties. The ability to control the amount of time the single radioactive source dwells at each position along the length of each brachytherapy catheter further enhances the conformity of the dose. In addition, recent radiobiologic data on prostate cancer treatment suggest that the α/β ratio for tumor control is similar to (or possibly even smaller) than that for surrounding late-responding normal tissues. If true, hypofractionation (as practiced with C-HDR BT combined with EBRT) would be expected to produce tumor control and late sequelae that are at least as good as achieved with conventional fractionation, with the additional possibility that early sequelae might be reduced. Recent data from several groups performing C-HDR BT in patients with locally advanced disease have confirmed these assumptions. Combined with the physical advantages discussed earlier, C-HDR BT as a means of dose escalation 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. The issues that remain unresolved with this technique (as with other methods of dose escalation) revolve around the amount of additional dose required to provide optimal tumor control, the role of androgen deprivation in the management of patients with locally advanced disease, and whether the regional lymphatics should be irradiated. © 2003 Elsevier Inc. All rights reserved.

The role of high-dose rate brachytherapy in locally advanced prostate cancer

Although the optimal management of patients with locally advanced prostate cancer remains undefined, sufficient clinical data have emerged showing that patients treated with radiation therapy (RT) have a significantly better outcome as the dose to the gland is escalated. What remains unresolved, however, is how to best deliver these higher tumoricidal doses of RT. Conformal high-dose rate brachytherapy (C-HDR BT) is an alternative means of precise dose escalation that offers similar tumoricidal effects as 3-dimensional (3D) conformal external beam radiotherapy (EBRT) with potential additional advantages. By placing HDR afterloading needles 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 unaffected by organ motion and edema or treatment setup uncertainties. The ability to control the amount of time the single radioactive source dwells at each position along the length of each brachytherapy catheter further enhances the conformity of the dose. In addition, recent radiobiologic data on prostate cancer treatment suggest that the alpha/beta ratio for tumor control is similar to (or possibly even smaller) than that for surrounding late-responding normal tissues. If true, hypofractionation (as practiced with C-HDR BT combined with EBRT) would be expected to produce tumor control and late sequelae that are at least as good as achieved with conventional fractionation, with the additional possibility that early sequelae might be reduced. Recent data from several groups performing C-HDR BT in patients with locally advanced disease have confirmed these assumptions. Combined with the physical advantages discussed earlier, C-HDR BT as a means of dose escalation 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. The issues that remain unresolved with this technique (as with other methods of dose escalation) revolve around the amount of additional dose required to provide optimal tumor control, the role of androgen deprivation in the management of patients with locally advanced disease, and whether the regional lymphatics should be irradiated.

Dose Escalation Using Conformal High Dose Rate Brachytherapy Improves the 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 HDR prostate brachytherapy was performed. We are reporting the outcomes. MaterialsM the high dose was 85% p = 0.001. There was improvement in cause-specific survival in favor of the brachytherapy high dose level p = 0.016. On multivariate analysis, a low dose level, higher Gleason score, shorter time to nadir and higher nadir value were associated with increased biochemical failure. RTOG grade 3 GI/GU complications ranged 0.5–9%. Actuarial 5 yr impotency rate was 52%. Conclusion: EBRT interdigitated with HDR prostate brachytherapy boost is a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on BC and cause-specific survival with higher doses. These results coupled with the low risk of complications and advantage of not being radioactive post-implant defines a new standard for treatment.

136 Phase II prospective study of the use of conformal high dose rate brachytherapy alone for the treatment of favorable stage prostate cancer patients

136 Phase II prospective study of the use of conformal high dose rate brachytherapy alone for the treatment of favorable stage prostate cancer patients

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont Phase II dose-escalating trial

Purpose: We analyzed our institution’s experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. Methods and Materials: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) ≥ 10.0 ng/ml, Gleason score ≥ 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2–7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Results: The pretreatment PSA level was ≥ 10.0 ng/ml in 51% of patients. The biopsy Gleason score was ≥ 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2–4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. Conclusion: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.

Normal tissue dosimetric comparison between hdr prostate implant boost and conformal external beam radiotherapy boost: potential for dose escalation

Purpose: To compare the dose and volume of bladder and rectum treated using high-dose-rate (HDR) prostate implant boost versus conformal external beam radiotherapy boost, and to use the dose–volume information to perform a critical volume tolerance (CVT) analysis and then estimate the potential for further dose escalation using HDR brachytherapy boost. Methods and Materials: Using CT scan data collected before and after patients underwent HDR prostate implant, a 7-field conformal prostate-only external beam treatment plan and HDR brachytherapy treatment plan were constructed for each patient. Doses to the normal structures were calculated. Dose–volume histograms (DVH) were plotted for comparison of the two techniques. Wilcoxon signed rank test was performed at four dose levels to compare the dose to normal structures between the two treatment techniques. The acute and late effects of HDR brachytherapy were calculated based on the linear-quadratic (LQ) model. CVT analyses were performed to calculate the potential dose gain (PDG) using HDR brachytherapy boost. Results: The volume of bladder and rectum receiving high dose was significantly less from implant boost. On the average, 0.19 cc of the bladder received 100% of the brachytherapy prescription dose, compared with 5.1 cc of the bladder receiving 100% of the prescription dose in the 7-field conformal external beam radiotherapy boost. Similarly, 0.25 cc of the rectum received 100% of the dose with the implant boost, as compared to 2.9 cc in the conformal external beam treatment. The implant also delivered higher doses inside the prostate volume. On average, 47% of the prostate received ≥150% of the prescription dose. The CVT analysis revealed a range of PDG using the HDR brachytherapy boost which depended on the following variables: critical volume (CV), critical volume tolerance dose (CVTD), number of HDR fractions (N), and the dose of external beam radiotherapy (XRT) delivered with brachytherapy boost. The PDG varied from −3.45% to 10.53% for tumor with an alpha–beta ratio of 10 and 7.14% to 64.6% for tumor with an alpha–beta ratio of 1.5 based on the parameters used for calculation in this study. Conclusions: HDR brachytherapy can provide better sparing of rectum and bladder while delivering a higher dose to the prostate. Even with the increased late effects of high dose per fraction, there is still a potential for dose escalation beyond external radiotherapy limits using HDR brachytherapy.

Ultrasound-guided high dose rate conformal brachytherapy boost in prostate cancer: Treatment description and preliminary results of a phase [formula omitted] clinical trial

To improve results for locally advanced prostate cancer, a prospective clinical trial of concurrent external beam irradiation and fractionated iridium-192 (Ir-192) high dose rate (HDR) conformal boost brachytherapy was initiated. Between November 1991 and February 1994, 99 implants were performed on 33 patients with prostatic adenocarcinoma at William Beaumont Hospital. Using AJCC staging criteria, 9 patients had T2b tumors, 17 patients had T2c tumors, and 7 patients had T3 disease. Patients were treated with (a) 45.6 Gy whole pelvis external irradiation and (b) three HDR fractions of 5.5 Gy each (18 patients) or 6 Gy each (15 patients) to the prostate. Transperineal needle implants using real-time ultrasound guidance with interactive on-line isodose distributions were performed on an outpatient basis during weeks 1, 2, and 3 of external irradiation. Acute toxicity was scored using the Radiation Therapy Oncology Group (RTOG) morbidity grading system. This technique of concurrent external pelvic irradiation and conformal HDR brachytherapy was well tolerated. No significant intraoperative or perioperative complications occurred. Three patients (9%) experienced Grade 3 acute toxicity (two dysuria and one diarrhea). All toxicities were otherwise Grades 1 or 2 and were primarily as expected from pelvic external irradiation. Persistent implant-related toxicities included Grades 1-2 perineal pain (12%) and hematospermia (15%). Median follow-up time was 13 months. Serum prostatic-specific antigen (PSA) levels normalized in 91% of patients (29 out of 32) within 1-14 months (median 2.8 months) after irradiation. PSA levels were progressively decreasing in the other three patients at last measurement. Prospectively planned prostatic rebiopsies done at 18 months in the first 10 patients were negative in 9 out of 10 (90%). Acute toxicity has been acceptable with this unique approach using conformal high dose rate Ir-192 boost brachytherapy with concurrent external irradiation. The initial tumor response as assessed by serial PSA measurement and rebiopsy is extremely encouraging. Dose escalation will proceed in accordance with the protocol guidelines. Further patient accrual and longer follow-up will allow comparison to other techniques.