Prostate brachytherapyA modelled comparison of prostate cancer control rates after high-dose-rate brachytherapy (3145 multicentre patients) combined with, or in contrast to, external-beam radiotherapy
Section snippets
Clinical material and data collection
Twenty-seven datasets were assembled from 10 institutions worldwide in Sweden, United States, Germany, United Kingdom, Brazil, Spain, Japan, and Australia. The institutions were different from those which supplied external-beam-alone data for the previous analysis [11]. All institutions were requested to provide recently updated information concerning the patients’ outcome (5-year bRFS according to the Phoenix or ASTRO criteria). Risk grouping was undertaken according to the National
Results
The expected dose-control curves for EBRT alone, along with the observed results for the combined HDR-BT treatments, are shown in Fig. 2. At lower values of EQD2, the observed results were within the range expected, although there was considerable variability. At higher values of EQD2, the observed results fell consistently well below the expected high levels of tumour control.
One way to look at this further is to use the outcome and external beam dose to predict what brachytherapy dose would
Discussion
The present analysis has shown that HDR brachytherapy prescription doses can produce the levels of prostate cancer control expected from LQ parameter value estimates deduced from external-beam-alone treatments, and this result is not altered over the range of α/β estimates compatible with the external beam data. However, this appears to be the case only when the BT component was less than 25 Gy in an EBRT + HDR-BT combined treatment, when BT doses per fraction were not more than 6 Gy, and when
Conflict of interest statement
None to declare.
Acknowledgements
The authors are very grateful to the following investigators for providing their primary data for this analysis: S. Aluwini (Rotterdam), R. Galalae (Kiel), P. Hoskin (Northwood), A. Pellizzon (Sao Paulo), P. Prada (Oviedo), J.L. Millar (Melbourne), Y. Yoshioka (Osaka). The study was partially financed by Fundació Privada Cellex. SAR acknowledges support from Central Manchester University Hospitals NHS Foundation Trust, and JHH from Christie Medical Physics and Engineering, The Christie NHS
References (27)
- et al.
Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer
Radiother Oncol
(2005) - et al.
High-dose-rate brachytherapy and external-beam radiotherapy for hormone-naïve low- and intermediate-risk prostate cancer: a 7-year experience
Int J Radiat Oncol Biol Phys
(2012) - et al.
High dose rate (HDR) brachytherapy with conformal radiation therapy for localized prostate cancer
Eur Urol
(2005) - et al.
Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer
Radiother Oncol
(2012) - et al.
High-dose-rate brachytherapy in combination with conformal external beam radiotherapy in the treatment of prostate cancer
Brachytherapy
(2010) - et al.
Monotherapeutic high-dose-rate brachytherapy for prostate cancer: five-year results of an extreme hypofractionation regimen with 54 Gy in nine fractions
Int J Radiat Oncol Biol Phys
(2011) - et al.
Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 (0.9–2.2) Gy
Int J Radiat Oncol Biol Phys
(2012) The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction
Semin Radiat Oncol
(2008)- et al.
A realistic closed-form radiobiological model of clinical tumor-control data incorporating intertumor heterogeneity
Int J Radiat Oncol Biol Phys
(1998) - et al.
In regard to Miralbell et al. Re: dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5969 patients in seven international institutional datasets: alpha/beta = 1.4 (0.9–2.2) Gy
Int J Radiat Oncol Biol Phys
(2013)
The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery
Semin Radiat Oncol
A challenge to traditional radiation oncology
Int J Radiat Oncol Biol Phys
Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results
Int J Radiat Oncol Biol Phys
Cited by (14)
Two-fraction stereotactic ablative radiotherapy (SABR) versus two-fraction high dose rate (HDR) brachytherapy for localized prostate cancer: Does dose heterogeneity matter?
2022, Radiotherapy and OncologyCitation Excerpt :However, some data suggest that for brachytherapy with very high EQD2, observed prostate cancer control rates can surprisingly fall below what would be expected. Hypothesized reasons for this contradictory finding included uncertainty with the linear-quadratic model at very high dose-per-fraction or even cold spots in the brachytherapy dose distribution [15]. Our present results for 2-fractions and a retrospective study comparing 4–5 fraction SABR vs 6 fraction HDR monotherapy showed no statistical differences in biochemical outcomes [16].
Progress in Low Dose Rate Brachytherapy for Prostate Cancer
2020, Seminars in Radiation OncologyCitation Excerpt :The principle advantage of the LDR approaches is continuous dose delivery for weeks or months from a single procedure, addressing tumor level resistance based in hypoxic, noncycling cells, or cells on the margin not encompassed by high dose initially but falling into the high-dose envelope as the tumor responds. Another purported advantage of HDR is the assertion that dose delivered versus planned dose is superior with HDR, which was called into question by a meta-analysis of greater than 3000 patients.55 Based on the presumed dose delivery, the failure rate was greater than predicted, and most consistent with either marginal miss or tumor level resistance.
Single fraction urethra-sparing prostate cancer SBRT: Phase I results of the ONE SHOT trial
2019, Radiotherapy and OncologyCitation Excerpt :How HDR-BT monotherapy findings overturning the LQ estimations for PCa can be applied to SBRT remains, however, a pending question. Uncertainties in disease control rates prediction by the LQ model with HDR-BT have been reported by Roberts et al., especially at higher doses [10]. In a retrospective series of 3145 PCa patients among 10 different institutions treated with HDR-BT alone or combined with EBRT, tumor control rates were lower than expected from LQ projections when HDR-BT dose were higher than 30 Gy, when doses per fraction were 9–15 Gy and the treatment was completed in only 1 week.
Single-dose high-dose-rate brachytherapy compared to two and three fractions for locally advanced prostate cancer
2017, Radiotherapy and OncologyCitation Excerpt :However recent results from randomized phase-III trials of external beam radiotherapy comparing hypofractionated with conventional scheduled [25,26] showed that modest hypofractionation was not superior to conventional radiotherapy and furthermore the RTOG study showed an increase in late adverse events with hypofractionation [26]. Our results and those of Krauss et al. [11] do not confirm what has been anticipated from analysis of animal data [23] and more recently clinical comparisons [22], that at higher EQD2, tumour control will be below the levels predicted by the LQ formulation. They also indicate that a single dose of 19–20 Gy achieves good levels of biochemical disease control with no suggestion of excess late morbidity compared to moderate hypofractionation.