High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence

doi:10.1016/j.ijrobp.2011.04.031

International Journal of Radiation OncologyBiologyPhysics

Volume 82, Issue 4, 15 March 2012, Pages 1376-1384

https://doi.org/10.1016/j.ijrobp.2011.04.031 Get rights and content

Purpose

To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone.

Methods and Materials

A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively.

Results

Incidence of early Grade ≥ 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, the highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p = 0.02).

Conclusions

There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good.

Introduction

Brachytherapy (BT) as permanent low-dose-rate (LDR) seed implants or high-dose-rate (HDR) after-loading has the ability to deliver a high localized radiation dose to the tumor, with excellent biochemical control of localized prostate cancer 1, 2. LDR-BT is most frequently used in low risk disease and HDR-BT as boost after external beam radiotherapy to treat intermediate and high-risk patients (for review, see Refs. 1 and 3). HDR-BT monotherapy has been primarily investigated in low-risk disease. Table 1 summarizes the studies that we have identified 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

The high sensitivity to dose fractionation of prostate adenocarcinomas 16, 17, which could be even lower than that of the rectum and urinary bladder (18), implies these tumors are more sensitive to large radiation doses per fraction than most other malignancies. Large fractions should maximize the cytotoxic dose to the tumor, and HDR-BT monotherapy should exploit this radiobiological advantage to the extreme. The expectation that hypofractionation will deliver a therapeutic gain is based on the low α/β ratios calculated using data that predominantly include patients with early prostate cancer. It is possible that more aggressive disease has lower sensitivity and therefore reduces the benefit from hypofractionation 19, 20. In addition, hypofractionation has a relatively greater effect on late-responding normal tissues and may result in unacceptable degrees of morbidity if the fractionation response of the tumor has lower sensitivity than the tissues in the treatment volume. Against this background, a dose escalation prospective Phase I/II study of HDR-BT monotherapy has been undertaken to evaluate early and late urinary and rectal morbidity and to evaluate biochemical control of disease. An earlier report involving 110 patients showed no detectable differences in incidence of early adverse events or that of late events at 6 and 12 months follow-up for total doses of 36 and 34 Gy in four fractions and 31.5 Gy in 3 fractions and good early biochemical control (21). The present report includes results of a further 87 patients, with an additional cohort receiving 26 Gy in two fractions and the earlier cohorts having more mature outcome data.

Section snippets

Patients and procedures

From November 2003 to July 2009, a total of 0197 patients with prostate adenocarcinoma were sequentially enrolled in this study, which was approved by the Hertfordshire Local Research Ethics Committee. Written informed consent was mandatory.

Patients with localized T1 to T3b tumors, staged by physical examination confirmed by pelvic magnetic resonance imaging (MRI) before entry, and a prostate-specific antigen (PSA) level <40 μg/l were included. A normal bone scan was mandatory for patients with

Results

Table 3 summarizes demographic characteristics and risk categories for the 197 patients in the study. As the median follow-up for patients treated with 26 Gy was 6 months, these patients were not included in the analysis of late morbidity or biochemical control.

Prevalence of early GU and GI adverse events was calculated for follow-ups on Weeks 1 to 14 after first implantation. Table 4 summarizes the highest incidence observed for Grade ≥2, Grade ≥3 and Grade 4 events. There were no Grade 3 or 4

Discussion

This Phase I/II study of HDR-BT as monotherapy has shown no significant difference in the extent and severity of urinary and rectal early and late radiation effects for doses per fraction of 8.5, 9, 10.5, and 13 Gy (early events only). This is not surprising, as the three higher doses per fraction were designed to have similar biological effectiveness in terms of late morbidity and for the 13 Gy per fraction to be equitoxic to the 4 × 8.5-Gy regimen for early effects. In addition, the patient

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Cited by (102)

High-dose-rate Brachytherapy Monotherapy in Patients With Localised Prostate Cancer: Dose Modelling and Optimisation Using Computer Algorithms
2024, Clinical Oncology
Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN).
Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BED_ef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BED_ef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models.
An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BED_ef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BED_ef = 279 Gy) by the RSM and ANN models.
The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime.
Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer
2023, Physics and Imaging in Radiation Oncology
Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT.
Calculated dose-volume indices between HDR-BT without a perirectal spacer (n = 20), robotic SBRT without a spacer (n = 40), and conventional (non-robotic) SBRT with a spacer (n = 40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared.
The D50% of the PTV with HDR-BT (140.5% ± 4.9%) was significantly higher than that with robotic or conventional SBRT (116.2% ± 1.6%, 101.0% ± 0.4%, p < 0.01). The D2cm³ of the bladder with HDR-BT (65.6% ± 6.4%) was significantly lower than those with SBRT (105.3% ± 2.9%, 98.0% ± 1.3%, p < 0.01). The D2cm³ of the rectum with HDR-BT (60.6% ± 6.2%) was also significantly lower than those with SBRT (85.1% ± 8.8%, 70.4% ± 9.6%, p < 0.01). By contrast, the D0.1cm³ of the urethra with HDR-BT (117.1% ± 3.6%) was significantly higher than those with SBRT (100.2% ± 0.7%, 104.5% ± 0.6%, p < 0.01).
HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.
Towards artificial intelligence-based automated treatment planning in clinical practice: A prospective study of the first clinical experiences in high-dose-rate prostate brachytherapy
2023, Brachytherapy
This prospective study evaluates our first clinical experiences with the novel ``BRachytherapy via artificial Intelligent GOMEA-Heuristic based Treatment planning'' (BRIGHT) applied to high-dose-rate prostate brachytherapy.
Between March 2020 and October 2021, 14 prostate cancer patients were treated in our center with a 15Gy HDR-brachytherapy boost. BRIGHT was used for bi-objective treatment plan optimization and selection of the most desirable plans from a coverage-sparing trade-off curve. Selected BRIGHT plans were imported into the commercial treatment planning system Oncentra Brachy . In Oncentra Brachy a dose distribution comparison was performed for clinical plan choice, followed by manual fine-tuning of the preferred BRIGHT plan when deemed necessary.
The reasons for plan selection, clinical plan choice, and fine-tuning, as well as process speed were monitored. For each patient, the dose-volume parameters of the (fine-tuned) clinical plan were evaluated.
In all patients, BRIGHT provided solutions satisfying all protocol values for coverage and sparing. In four patients not all dose-volume criteria of the clinical plan were satisfied after manual fine-tuning. Detailed information on tumour coverage, dose-distribution, dwell time pattern, and insight provided by the patient-specific trade-off curve, were used for clinical plan choice. Median time spent on treatment planning was 42 min, consisting of 16 min plan optimization and selection, and 26 min undesirable process steps.
BRIGHT is implemented in our clinic and provides automated prostate high-dose-rate brachytherapy planning with trade-off based plan selection. Based on our experience, additional optimization aims need to be implemented to further improve direct clinical applicability of treatment plans and process efficiency.
Brachytherapy focal dose escalation using ultrasound based tissue characterization by patients with non-metastatic prostate cancer: Five-year results from single-center phase 2 trial
2022, Brachytherapy
This prospective trial investigates side effects and efficacy of focal dose escalation with brachytherapy for patients with prostate cancer.
In the Phase II, monocentric prospective trial 101 patients with low-/intermediate- and high-risk prostate cancer were enrolled between 2011 and 2013. Patients received either PDR-/HDR-brachytherapy alone with 86–90 Gy (EQD2, α/β = 3 Gy) or PDR-/HDR-brachytherapy as boost after external beam radiation therapy up to a total dose of 91–96 Gy (EQD2, α/β = 3 Gy). Taking place brachytherapy all patients received the simultaneous integrated focal boost to the intra-prostatic tumor lesions visible in computer-aided ultrasonography (HistoScanning™) - up to a total dose of 108–119 Gy (EQD2, α/β = 3 Gy). The primary endpoint was toxicity. Secondary endpoints were cumulative freedom from local recurrence, PSA-free survival, distant metastases-free survival, and overall survival. This trial is registered with ClinicalTrials.gov, number NCT01409876.
Median follow-up was 65 months. Late toxicity was generally low with only four patients scoring urinary grade 3 toxicity (4/101, 4%). Occurrence of any grade of late rectal toxicities was very low. We did not register any grade ≥2 of late rectal toxicities. The cumulative 5 years local recurrence rate (LRR) for all patients was 1%. Five years- biochemical disease-free survival estimates according Kaplan-Meier were 98,1% and 81,3% for low-/intermediate-risk and high-risk patients, respectively. Five years metastases-free survival estimates according Kaplan-Meier were 98,0% and 83,3% for all patients, low-/intermediate-risk and high-risk patients, respectively.
The 5 years-results from this Phase II Trial show that focal dose escalation with computer-aided ultrasonography and brachytherapy for patients with non-metastatic prostate cancer is safe and effective.
A comparative study of patient-reported outcomes after contemporary radiation techniques for prostate cancer: QOL comparison of modern radiotherapy techiques
2022, Radiotherapy and Oncology
We aim to compare health-related quality of life (HRQoL) deterioration at 12 months in low-and intermediate-risk prostate cancer (PCa) patients treated with stereotactic ablative radiotherapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost.
Patients treated as part of 7 prospective clinical trials were included. All patients had low-or intermediate-risk PCa. Three strategies were considered: SABR, HDR monotherapy and HDR boost. HRQoL was prospectively measured at baseline and 12 months in all trials, using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline ≥0.5 standard deviation of baseline score. Univariate and multivariable logistic regression using generalized estimating equations were used to compare the proportion of patients having MID between groups. A set of sensitivity analyses was conducted.
648 patients were included: 288, 173 and 187 respectively in the SABR, HDR monotherapy and HDR boost group. On univariate and multivariable analyses, SABR and HDR monotherapy compared to HDR boost, were associated with less deterioration in the urinary (38%, 40% vs. 55%; OR:0.543, 95%CI:0.320–0.922, p = 0.024; OR:0.468, 95%CI:0.432–0.507, p < 0.001) and sexual domains (38%, 42% vs. 47%; OR:0.762, 95%CI:0.645–0.900, p = 0.001; OR: 0.786, 95%CI:0.650–0.949, p = 0.012). These findings were robust to a variety of sensitivity analyses.
Recent monotherapeutic approaches for low- and intermediate-risk PCa are associated with the preservation of patients HRQoL. Ultimately, the questions of efficacy, toxicity, and HRQoL will be best answered by a randomized clinical trial.
GEC-ESTRO ACROP prostate brachytherapy guidelines
2022, Radiotherapy and Oncology
Citation Excerpt :
Gland size: previous guidelines have recommended limits of 50–60 ml however for both LDR and HDR, if there is minimal pubic arch interference, there is now published data showing that much larger glands can be successfully implanted with good results for both dosimetry and biochemical control with no excess toxicity [5,6]. Locally advanced prostate cancer (stage T3): There are now published data showing good oncological outcomes when stage T3a and T3b cancers are treated with either LDR or HDR brachytherapy boost [7,8]. Outflow obstruction: with due attention to dose distribution patients having had previous intervention for outflow obstruction eg.
This is an evidence-based guideline for prostate brachytherapy. Throughout levels of evidence quoted are those from the Oxford Centre for Evidence based Medicine (https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009).
Prostate interstitial brachytherapy using either permanent or temporary implantation is an established and evolving treatment technique for non-metastatic prostate cancer.
Permanent brachytherapy uses Low Dose Rate (LDR) sources, most commonly I-125, emitting photon radiation over months. Temporary brachytherapy involves first placing catheters within the prostate and, on confirmation of accurate positioning, temporarily introducing the radioactive source, generally High Dose Rate (HDR) radioactive sources of Ir-192 or less commonly Co-60. Pulsed dose rate (PDR) brachytherapy has also been used for prostate cancer [1] but few centres have adopted this approach. Previous GEC ESTRO recommendations have considered LDR and HDR separately [2–4] but as there is considerable overlap, this paper provides updated guidance for both treatment techniques.
Prostate brachytherapy allows safe radiation dose escalation beyond that achieved using external beam radiotherapy alone as it has greater conformity around the prostate, sparing surrounding rectum, bladder, and penile bulb. In addition there are fewer issues with changes in prostate position during treatment delivery. Systematic review and randomised trials using both techniques as boost treatments demonstrate improved PSA control when compared to external beam radiotherapy alone [5–7].

View all citing articles on Scopus

: Supported by the Cancer Research Fund, Mount Vernon Hospital, Northwood, Middlesex, UK.

: Conflicts of interests: none

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Clinical InvestigationHigh-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Patients and procedures

Results

Discussion

Radiother Oncol

Clin Oncol (R Coll Radiol)

Int J Radiat Oncol Biol Phys

Brachytherapy

Brachytherapy

J Urol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Brachytherapy

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clin Oncol (R Coll Radiol)

Int J Radiat Oncol Biol Phys

Clinical Investigation
High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence