scholarly journals High-Dose-Rate Brachytherapy as Monotherapy for Low- and Intermediate-Risk Prostate Cancer. Oncological Outcomes After a Median 15-Year Follow-Up

2021 ◽  
Vol 11 ◽  
Author(s):  
Manuel Behmueller ◽  
Nikolaos Tselis ◽  
Nikolaos Zamboglou ◽  
Eleni Zoga ◽  
Dimos Baltas ◽  
...  

IntroductionTo evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA).Material and MethodsBetween January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0.ResultsMedian age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS.ConclusionOur long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15571-15571
Author(s):  
B. Guix ◽  
J. Bartrina ◽  
I. Henriquez ◽  
R. Serrate ◽  
P. Palombo ◽  
...  

15571 Background: To report early and late toxicity and preliminary biochemical outcome in 345 patients with high-risk (Gleason >=7; PSA>20 or T2c-T3) clinically localized prostate cancer treated with combined high-dose-rate brachytherapy and IMRT (IMRT-HDR) to the prostate and seminal vesicles with 24–36 months of hormononal treatment (goserelin+bicalutamide) (HT). Methods: Between 12/1999 and 10/2003, 345 patients with PSA>20, Gleason score>6 and/or T2c-T3 N0 M0 prostate cancer were treated with IG-IMRT followed by HDR implant to the prostate and HT. Patients were randomly assigned to receive HT for 24 (group 1, 172 patients) or 36 months (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. PSA failure was defined as nadir +2.0 ng/ml. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Seven patients in each group (4.0%) developed acute Grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed Grade 4 rectal complications or grade 3 or 4 urinary complications. With a median follow-up of 44 months, the 5-year actuarial PSA relapse-free survival rates for the whole group of patients was 95.7 %. No statistical differences between group 1 and 2 patients were found. Conclusions: High-dose IG-IMRT+HDR and HT was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly low, compared with what has been observed with high-dose conventional, 3D-conformal or IMRT-only. Short-term PSA control rates seem to be at least comparable to those achieved with 3D-EBRT or IMRT. Both treatment regimes were very effective. Longer follow-up is needed to know if better PSA control rate are achieved with longer HT. No significant financial relationships to disclose.


2015 ◽  
Vol 15 (1) ◽  
pp. 23-29
Author(s):  
John K. L. Chin ◽  
Kenanao D. Rantshilane ◽  
Paul K. L. Chin ◽  
Anupam Chaudhuri ◽  
Leanne K. Tyrie ◽  
...  

AbstractAimThe aim of the present study was to report the survival outcomes and late toxicity of high-dose-rate brachytherapy (HDRBT) boost for dose escalation in patients with intermediate-to-high-risk prostate cancer.Materials and methodsRetrospective data were collected from 137 patients who had undergone definitive radiotherapy for prostate cancer between 2006 and 2010. All patients had external-beam radiotherapy (median dose 46Gy) and HDRBT. Brachytherapy dose was 19Gy in two fractions (6 hours apart) with one implant using Ir-192.ResultsThere were 94 high-risk and 43 intermediate-risk patients (NCCN classification). The median follow-up period was 60 months. The 5-year biochemical progression-free survival was 92 and 76% for intermediate- and high-risk groups, respectively. Prostate cancer-specific survival for the intermediate-risk group was 100% and for the high-risk group it was 92% at 5 years. For the entire cohort, the 5-year rate of urethral stricture formation was 13%, and the 5-year rate of late grade 2 and grade 3 gastrointestinal toxicity was 4·7 and 4·6%, respectively. There was no grade 3 or greater genitourinary toxicity.FindingsOur data add to the growing body of literature supporting the use of HDRBT in prostate cancer. Late toxicity rates were marginally higher than that expected.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 301-301
Author(s):  
Trude Wedde ◽  
Milada Cvancarova ◽  
Jonathan S. Hayman ◽  
Phuoc T. Tran ◽  
Gunnar Tafjord ◽  
...  

301 Background: The aim is to investigate the clinical significance of biochemical response after Androgen Deprivation Therapy (ADT) prior to high-dose-rate brachytherapy (HDR-BT) for early identification of patients at increased risk of recurrence. Measured outcomes included biochemical relapse free survival (bRFS), distant metastasis free survival (DMFS) and overall survival (OS). Methods: A total of 324 patients with high-risk Prostate Cancer (PCa) were identified in the Norwegian Radium Hospital brachytherapy database. Neo-adjuvant ADT was administered for 3-6 months, followed by two 10 Gy HDR-BT treatments to the prostate, each spaced by two weeks, followed by conformal external beam radiation to 50 Gy to the prostate gland and seminal vesicles. Total length of ADT ranged from 12 to 36 months. PSA (ng/mL) and testosterone values (T, nmol/L) after 3-6 months of neo-adjuvant ADT were measured. Kaplan Meier and Cox regression analyses were performed. Results: Median age at diagnosis was 66 years and median follow-up was 10 years. At last follow-up, 277 patients (85,2%) were alive, 10 patients (3.1%) had died of prostate cancer and 37 patients (11.4%) died of other causes. 24 patients (7.4%) had biochemical relapse and 9 patients (2.8%) had distant metastasis within the first 5 years. Patients with PSA > 1 after neo-adjuvant therapy had 4.3 (95%CI 1.7 to 11.1) higher odds of biochemical relapse within 5 years compared to patients with PSA < 1 (p = 0.002). ROC analysis confirmed that PSA < 1 had a prediction accuracy of 0.76 (sensitivity 68% and specificity 67%). T < 0.7 and PSA < 1 after neo-adjuvant therapy were associated with improved bRFS, DMFS and OS (p < 0.001). Neither the length of neo-adjuvant nor total ADT treatment impacted outcomes (p > 0.05). Conclusions: Dose intensification with 2 HDR-BT boosts resulted in excellent survival in our cohort. PSA > 1 after neo-adjuvant ADT may be able to predict patients at increased risk of relapse and worse OS and identify patients in whom increased monitoring and/or intervention is warranted. ADT > 1 year did not improve outcome, indicating that shorter course of ADT may be used.


2012 ◽  
Vol 11 (4) ◽  
pp. 257-270
Author(s):  
Mutahir A. Tunio ◽  
Altaf Hashmi ◽  
Amjad Sattar ◽  
Rehan Mohsin ◽  
Shoukat Ali ◽  
...  

AbstractPurpose: Recent studies have shown increased prostate cancer control rates with radiation dose escalation. Herein the experience of dose escalation by high dose rate brachytherapy (HDR-BT) adjunct to the three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer is presented.Patients and methods: During the period between August 2005 and July 2007, patients with intermediate and high risk prostate cancer were treated with 3D-CRT of dose 46Gy ÷ 23 fractions to whole pelvis followed by: Arm A (102 patients): prostate boost with HDR-BT 14 Gy × 2 sessions and Arm B (103 patients): prostate boost via 3D-CRT of dose 26 Gy ÷ 13 fractions. Primary objectives were overall survival (OS), distant metastases free survival (DMFS) and PSA progression free survival (PPFS) rates. Secondary objectives were the toxicity profile and post-radiation histopathological response.Results: At median follow up of 3.5 years, PPFS, DMFS and OS rates were; 97.8% versus 89.0% (p = 0.009), 98.1% versus 93.6% (p = 0.13) and 98.8% versus 91.6% (p = 0.24) in Arm A and Arm B. respectively. Grade 3 or 4 delayed genitourinary toxicities occurred in 2% and 4.8% of patients in Arm A and Arm B, respectively. Delayed grade 3 and 4 gastrointestinal toxicities were seen in 2% and 3.9% of patients in Arm A and Arm B, respectively. The post-radiation prostate biopsies were negative in 14/17(82.3%) and 9/15 (60%) in Arm A and Arm B, respectively.Conclusion: 3D-CRT combined with HDR-BT resulted in better PPFS and lower morbidity than 3DCRT alone for intermediate and high risk prostate cancer.


2021 ◽  
Vol 17 (2) ◽  
pp. 72-82
Author(s):  
V. A. Solodkiy ◽  
A. Yu. Pavlov ◽  
A. D. Tsibulskii ◽  
G. A. Panshin ◽  
A. G. Dzidzaria ◽  
...  

Background. Prostate cancer (PCa) in the Russian Federation takes the leading place in the prevalence of cancer among the male population.Objective: to investigate the effect of increasing a single focal dose in high-dose-rate brachytherapy (HDR-BT) in combination with external beam radiotherapy on biochemical failure-free survival and local control in patients with high-risk PCa. Materials and methods. The study included 350 men with PCa in the group of high and extremely high risk of progression. All patients included in the study were divided into 4 groups. Groups 1, 2 and 3 included 276 patients who received HDR-BT with a 192Ir source with a single dose per fraction: 10 Gy (n = 83), 12 Gy (n = 46) and 15 Gy (n = 147). Group 4 included 74 patients who received low-dose-rate brachytherapy with 125I sources up to a total focal dose of 110 Gy. At the 2 stage, external beam radiotherapy was a conventional fractionation (single dose of 2 Gy, total - 44-46 Gy).Results. Of 350 patients over a 5-year follow-up period, PCa recurrence was noted in 65 (18.6 %). The 3- and 5-year biochemical failure-free survival rates in the general cohort of patients were 87.4 and 81.4 %. 5-year biochemical failure-free survival was significantly higher in group 3 relative to group 4 and amounted to 89.8 and 74.2 % (p = 0.03). Increasing the dose for HDR-BT from 10 to 12 Gy per fraction significantly reduced the frequency of local relapses from 15.7 % (in group 1) to 2.2 % (in group 2) (p = 0.0001) while maintaining the level of genitourinary and gastrointestinal toxicity. Conclusion. The use of a combination of brachytherapy and external beam radiotherapy in patients with high risk PCa is highly effective in achieving local control of the tumor. The optimal fractionation regime for HDR-BT remains a matter of debate. The use of 15 Gy per fraction for HDR-BT in combination with external beam radiotherapy is the most optimal fractionation regimen in patients with high-risk PCa.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 365-365
Author(s):  
Irving D. Kaplan ◽  
Limor Appelbaum ◽  
Nima Aghdam ◽  
Jarad Martin ◽  
Mark Sidhom ◽  
...  

365 Background: External beam radiation therapy (EBRT) with androgen suppression (AS) and low dose rate (LDR)brachytherapy boost has been shown to improve biochemical progression free survival in unfavorable intermediate risk and high-risk prostate cancer (PC) compared to EBRT and AS. Excellent rates of local control in locally advanced prostate cancer with EBRT with high dose rate brachytherapy (HDR) boost. Prostate Stereotactic Radiosurgery (SBRT) may be an alternative to brachytherapy in patients with unfavorable intermediate and high-risk PC. Here we report the toxicity of pelvic lymph node/prostate EBRT and SBRT as the radiation boost in a large retrospective cohort. Methods: 473 patients with intermediate or high-risk PC, from the Radiosurgery Society Registry, Beth Israel Deaconess Medical Center, Georgetown University, and 5 Australian centers, were included. Patients received treatment from 3/2004- 9/2018 were the basis of this IRB approved retrospective study. The prostate and pelvis nodes were treated with between 36-50.4 Gy in 1.8/2.0 Gy fractions of radiation therapy EBRT. Patients received a SBRT boost to the prostate. Boost dose was 19-19.5 Gy (range 19-36.25 Gy). 274 and 199 patients presented with unfavorable or high-risk disease. The median follow-up was 33 months (IQR:18-63). Results: 33 deaths of 473 patients occurred in this cohort, 8 of which were caused by PC. There were 13.9% (n=66) acute Grade 1 or 2 GI toxicities (11.8% grade 1, 2.1% grade 2). There were 27.7% (n=131) acute Grade 1 or 2 GU toxicities (19.2% grade 1, 8.5% grade 2). No severe acute GU or GI toxicities were reported. There were 32 (6.8%) Grade 1 and 3 (0.6%) Grade 2 late GI toxicities. There were 9 (1.9%) Grade 3 and 1 (0.2%) Grade 4 late GI toxicities. There were 60 (12.7%) Grade 1 and 23 (4.9%) Grade 2 late GU toxicities. 15 (3.2%) Grade 3, but no Grade 4 late GU toxicity were reported. Conclusions: In this large multi-institutional retrospective cohort SBRT boost to pelvic/prostate EBRT had acceptable acute and late toxicities. The high dose per fraction of SBRT is similar to the dose delivered with HDR. This data raises the hypothesis that SBRT boost should be evaluated in additional clinical trials.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 236-236
Author(s):  
Imtiaz Ahmed ◽  
Sharon Shibu Thomas ◽  
Alexander Cain ◽  
Jufen Zhang ◽  
Sreekanth Palvai ◽  
...  

236 Background: Advances in brachytherapy, external beam radiotherapy (EBRT) and image-guided radiotherapy have revolutionized radiotherapy delivery. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities remain a significant issue. Currently there is no European consensus on the timing of high-dose rate (HDR) brachytherapy in relation to EBRT. Schedules of HDR boost before or after EBRT vary significantly between institutions.The incidence of GI and GU toxicities was assessed in patients receiving HDR brachytherapy before and after EBRT. Methods: Men with Intermediate/high risk localized prostate cancer were randomized to Arm A (HDR brachytherapy before EBRT) or Arm B (HDR brachytherapy after EBRT). Both arms received a HDR boost of 15Gy and 46Gy in 23 fractions of EBRT. All patients received neoadjuvant and adjuvant hormone therapy for up to 2 years. Patients were followed quarterly up to a year. CTCAE scores for GU and GI toxicities were taken. IPSS, IEFL and FACT-P scores were collected. Fisher’s exact test was used to analyze the association between GU and GI toxicities. The T-test compared the mean differences in IPSS total scores at each follow-up. Analysis of variance evaluated the difference at follow up. Post-hoc testing and Bonferroni correction was applied. Results: 100 patients were randomized between 2015 and 2017. Data for 88 patients was available at cutoff. Mean age was 69 years (SD: 4.6). Age, Gleason score, TNM and clinical staging were similar in each arm. Mean IPSS Score was similar between both arms at baseline Arm A (6.52) & Arm B (6.57). 12 months follow up showed mild worsening of symptoms in both arms, but no significant difference noticed between Arm A (8.02) & Arm B (8.14) p=0.55. At 12 months, Grade 1 and 2 GU toxicities were more frequent in Arm A (22.88% & 5.28%, p=0.669) compared to Arm B (19.36% and 2.64%, p=0.485). Grade 1 GI toxicity was more common in Arm B (23.76%) than Arm A (21.2%), p=0.396. Grade 2 GI toxicities were more common in Arm A 5.28% vs 3.52%, p=0.739. Baseline mean IIEF scores were 10.9 and 10.53 in Arm A and B respectively. At 12 months this was 6.6 in Arm A and 7.11 in Arm B, but not statistically significant. FACT-P scores were not different in either arm, with good QOL scores maintained throughout. Mean score at baseline (125.18) was observed to be similar at 12 months follow up at (126.10). The PTV, CTV & OAR dose were compared and no significant differences were found. Conclusions: There were no significant differences in GI and GU related toxicities up to a year between patients receiving HDR brachytherapy before or after EBRT. There were no grade 3 or 4 toxicities. Treatment was well tolerated in both arms with good QOL scores. Longer follow up and a phase III multicenter RCT would be needed to validate findings. Clinical trial information: NCT02618161.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14633-14633
Author(s):  
R. J. Mark ◽  
P. J. Anderson ◽  
T. Neumann ◽  
M. Nair

14633 Background: Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) technique has been reported with results comparing favorably to surgery and External Beam Radiation Therapy (EBRT). Often, HDR and LDR interstitial implant is combined with EBRT. There is little published data on HDR alone. We report our results with HDR alone. Methods: Between 1997 and 2006, 167 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant. There were no Gleason Score or PSA exclusions. No patient received EBRT or Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.3 (2.7 to 39.8). Treatment volumes ranged from 42 cm3 to 196 cm3. Treatment volume included the prostate and seminal vesicles in all cases. Our protocol for HDR alone, has called for two HDR Implants. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12–16) were followed, and limited to ≤ 105% of the prescription dose. Results: With a median follow-up of 64 months (range: 6 months to 112 months), PSA disease free survival was 89.8% (150/167). Urethral stricture requiring dilatation has developed in 4.2% (7/167) of patients. Urinary stress incontinence has occurred in 3.6% (6/167). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.6% (6/167) Grade 2. RTOG late rectal toxicities were: 0.6% (1/167) Grade 4, 0% Grade 3, 1.8% (3/167) Grade 2, and 2.4% (4/167) Grade 1. There have been no cases of rectal incontinence to date. Conclusions: Five year results with HDR implant alone compare favorably to EBRT, LDR ± EBRT, and HDR + EBRT, both with regard to PSA disease free survival, and complications. HDR offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, bladder and rectal complications appear to be significantly reduced. No significant financial relationships to disclose.


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