Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer (original) (raw)
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Clinical & Translational Oncology, 2005
Introduction It has been well documented that the outcome of prostate cancer treatment depends on the dose administered. Hence, techniques have been developed that allow high-dose administration without increasing the complications, e.g. external radiotherapy combined with high-dose radiation (HDR) brachytherapy. In this article we analyse the technique and protocol of real-time HDR brachytherapy together with the preliminary results that support its use. Materials and methods Between June 1998 and December 2004, 100 patients with adenoma of the prostate were treated with 46 Gy of external irradiation to the pelvis and 2 HDR brachytherapy fractions (each of 1150 cGy) at the end of weeks 1 and 3 of a 5-week radiotherapy course. The 1997 American Joint Commission on Cancer (AJCC) system was used to establish disease stage. Patients with intermediaterisk (PSA 10–20 ng/ml or Gleason=7 or T2c) and high-risk (two intermediate risk factors or PSC >20 ng/ml or Gleason >7 or >T2c) without metastases were eligible for the brachytherapy. Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus panel statement. SPSS statistical package was used to quantify survival (Kaplan-Meier method). Toxicity was scored according to RTOG guidelines. Results The mean age of patients was 67 years (range 49–78). Clinical stage was T2a in 22% of the patients, 26% T2b and 52% T3. Initial PSA was = 10 ng/ml in 22% of the patients and >10 ng/ml in 78%. Median follow-up was 28 months (range: 12–79). The 5-year overall survival and actuarial biochemical control were 99% and 87% respectively. No chronic severe complications were noted. Conclusions The good results of local control, disease-free survival and few complications that the external radiotherapy combined with HDR brachytherapy have shown suggest that the method should be considered as first-choice in the treatment of prostate tumours of high-and intermediate-risk.
Brachytherapy, 2014
PURPOSE: Dose escalation using high-dose-rate brachytherapy (HDR-BT) is an established treatment method for prostate cancer. First, long-term results were previously published (specific Kiel method). This study aims to evaluate 10-/15-year outcomes of Kiel Protocol 1 (1986e1992). METHODS AND MATERIALS: Conformal external beam radiotherapy (EBRT) was delivered to the pelvis (50 Gy per conventional fractionation) along with an HDR boost to the prostate amounting to a combined biologic equivalent dose in 2 Gy per fraction of 117.25 Gy (a/b 5 3). The HDR-BT was performed in two fractions of 15 Gy to the peripheral zone of McNeal. The EBRT-clinical target volume covered the full pelvis. The analyzed cohort totaled 122 patients. The reported end points were overall/cancer-specific survival, local recurrence/distant metastasis rates, and biochemical (BC) control rates according to American Society for Therapeutic Radiology and Oncology/Phoenix definitions. All end points were calculated using the KaplaneMeier method and the log-rank test in univariate analyses. RESULTS: The mean follow-up time was 116.8 months. The 5-, 10-, and 15-year survival rates were 81%, 62.1%, and 45% for overall survival; 92.1%, 83.1%, and 75.3% for cancer-specific survival; 92.5%, 91.4%, and 83.9% for local recurrenceefree survival; and 83.8%, 81.2%, and 69.8% for distant metastasisefree survival, respectively. American Society for Therapeutic Radiology and Oncologyedefined BC tumor control rates at 5, 10, and 15 years were 81.1%, 74%, and 67.8%, respectively. According to Phoenix, the BC control rates at 5, 10, and 15 years were 77.8%, 69%, and 63.6%, respectively. CONCLUSIONS: The long-term results for the combination of HDR-BT and EBRT continue to show excellent results, providing high equivalent dose in 2 Gy per fraction and high disease control rates. These outcomes were reproducible for the extended follow-up period ranging up to 21.9 years.
International Journal of Radiation Oncology*Biology*Physics, 2011
De uitgave van dit proefschrift werd mede mogelijk gemaakt door steun van AstraZeneca, Best Medical International, CurieMed, Emnovation, Elekta, Ella-CS en Nucletron. intRoduction intRoduction 13 temPoRaRy PRostate imPlants Brachytherapy for prostate cancer can be applied by permanent or temporary implants. Nowadays the most often used isotopes for permanent prostate implants are I-125 and Pd-103. Good treatment results have been reported resulting in a high acceptance as efficacious treatment modality worldwide [38-41]. Radioactive seeds are implanted directly into the prostate gland and remain there for the rest of patient's life. The effective dose is delivered during several weeks or months depending on the radioactive decay. A different approach for brachytherapy is by temporary implants. Radioactive source(s) are placed into the prostate via needles or catheters. After the required dose has been applied, the source(s) and the needles/catheters are removed. The most developed and popular technique is with an HDR Ir-192 source [25]. Accurate positioning of the source is possible by placing first non-active needle/catheters. With an interactive treatment planning system a virtual dose distribution can be obtained which allows the possibility for needle/catheter position adjustments. Small imperfections of needle/catheter positioning can be adjusted with dwell time optimization techniques. An advantage of afterloading HDR brachytherapy is that there is no radiation exposure to medical personnel and other people. A disadvantage of HDR brachytherapy for prostate cancer compared to a permanent implant is the need for fractionated treatment. This means that a patient has to be hospitalized for several days or multiple implantation sessions should be planned. PdR PRostate BRachytheRaPy PDR prostate brachytherapy was introduced at the AMC in 2002 [37]. In contrast to the high source activity used for HDR (approximately 370 GBq), in PDR a source of 18.5 -74 GBq is used. With PDR multiple small size fraction doses can be given in several hours or days. Because PDR brachytherapy uses the same stepping source technology as HDR, the same technical and physical features are applicable, such as virtual treatment planning, afterloading with no radiation exposure to other people, and dwell time optimization. However, different from HDR, the multifractionated dose delivery in PDR mimics a radiation course of LDR. The concept of PDR was proposed by Brenner and Hall to combine the features of a stepping source treatment with LDR treatment [42].
Acta Oncologica, 2007
To report the long-term results for treatment of localized carcinoma of the prostate using high dose rate (HDR) brachytherapy, conformal external beam radiotherapy (3D EBRT) and neo-adjuvant hormonal therapy (TAB). From 1998 through 1999, 154 patients with localized prostate cancer were entered in the trial. Biologically no evidence of disease (bNED) was defined at PSA levelsB/2 mg/l. In order to compare the results of this treatment with other treatment modalities, the patient's pre-treatment data were used to calculate the estimated 5-year PSA relapse free survival using Kattan's nomograms for radical prostatectomy (RP) and 3D EBRT. After 6 years of follow-up, 129 patients remain alive. The actual 5-year relapse-free survival is 84%. None of the patients demonstrated clinical signs of local recurrence. The median PSA at follow-up among the relapse-free patients was 0.05 mg/l. Among the 80 patients who presented with clinical stage T3 tumours, 55 (68%) were relapse-free. The expected 5-year relapse-free survival using nomograms for RP and 3D EBRT was 54% and 70%, respectively. Late rectal toxicity RTOG grade 3 occurred in 1% of the patients. Late urinary tract toxicity RTOG grade 3 developed in 4% of the patients. Combined treatment, utilizing HDR, 3D EBRT and TAB, produces good clinical results. Rectal toxicity is acceptable. Urinary tract toxicity, most likely can be explained by the fact that during the first years of this treatment, no effort was made to localize the urethra, which was assumed to be in the middle of the prostate. Acta Oncologica, 2007; 46: 909 Á917
International Journal of Radiation Oncology*Biology*Physics, 2010
To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with ≥18 months of potential follow-up. A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level ≤10 ng/mL, 70%; prostate-specific antigen level >10 but ≤20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.
Brachytherapy, 2013
To report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer. METHODS AND MATERIALS: Between 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of 192 Ir (5.5e7.5 Gy per fraction), and EBRT consisted of intensitymodulated radiotherapy delivering an additional 45.0e50.4 Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months. RESULTS: Seven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p!0.001). Among high-risk patients treated with biological equivalent doses in excess of 190 Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of $8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate-or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Sevenyear incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively. CONCLUSION: HDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort.
International Journal of Radiation Oncology*Biology*Physics, 2012
Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy  4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy  2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years.
Brachytherapy, 2011
PURPOSE: To analyze the clinical outcome and toxicity data of the first 100 consecutive patients treated with a single-fraction highedose rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT). METHODS AND MATERIALS: Two-hundred eighty patients have been treated with HDR-BT boost for localized intermediate-to high-risk prostate cancer. Among these, the outcome and toxicity of the first 100 patients treated with a single HDR-BT fraction were assessed. A median dose of 60 Gy EBRT was given to the prostate and vesicles. Interstitial HDR-BT of 10 Gy was performed during the course of EBRT. RESULTS: Median followup time was 61.5 months. The 5-year actuarial rates of overall survival, cause-specific survival, disease-free survival, and biochemical no evidence of disease (bNED) for the entire cohort were 93.3%, 99.0%, 89.3%, and 85.5%, respectively. The 7-year actuarial rate of bNED was 84.2% for the intermediate-risk group and 81.6% for the high-risk group ( p 5 0.8464). The 7-year actuarial rates of bNED for Grade 1, 2, and 3 tumors were 97.5%, 80.0%, and 67.1%, respectively. The 5-year probability for developing late Grade 3 gastrointestinal and genitourinary (GU) toxicity was 2.1% and 14.4%, respectively. Grade 3 GU complications occurred significantly more frequently in patients with a history of preirradiation transurethral resection (29.1% vs. 8.8%; p 5 0.0047). CONCLUSIONS: Five-year outcome after 60 Gy EBRT plus a single fraction of 10 Gy HDR-BT boost is encouraging. Preradiation transurethral resection significantly increases the risk of late severe GU complications. Ó
Critical reviews in oncology/hematology, 2015
The intrinsic physical and radiobiological characteristics of High Dose Rate Brachytherapy (HDR-BT) are well suited to the treatment of prostate cancer. HDR-BT was initially used as a boost to external beam brachytherapy, but has subsequently been employed as the sole treatment, which is termed HDR monotherapy. This review summarizes the clinical outcomes and toxicity results of the principal studies and discusses the radiobiological basis supporting its use.