Prostate brachytherapy
A modelled comparison of prostate cancer control rates after high-dose-rate brachytherapy (3145 multicentre patients) combined with, or in contrast to, external-beam radiotherapy

https://doi.org/10.1016/j.radonc.2014.01.008Get rights and content

Abstract

Background and purpose

To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combined external beam and high-dose-rate brachytherapy, in comparison with expected results using projections based on dose/fractionation/response parameter values deduced from a previous external-beam-alone 5969-patient multicentre dataset.

Material and methods

Results on a total of 3145 prostate cancer patients receiving brachytherapy (BT) as part or all of their treatment were collected from 10 institutions, and subjected to linear-quadratic (LQ) modelling of dose response and fractionation parameters.

Results

Treatments with BT components of less than 25 Gy, 3–4 BT fractions, doses per BT fraction up to 6 Gy, and treatment times of 3–7 weeks, all gave outcomes expected from LQ projections of the external-beam-alone data (α/β = 1.42 Gy). However, BT doses higher than 30 Gy, 1–2 fractions, 9 fractions (BT alone), doses per fraction of 9–15 Gy, and treatment in only 1 week (one example), gave local control levels lower than the expected levels by up to ∼35%.

Conclusions

There are various potential causes of the lower-than-projected control levels for some schedules of brachytherapy: it seems plausible that cold spots in the brachytherapy dose distribution may be contributory, and the applicability of the LQ model at high doses per fraction remains somewhat uncertain. The results of further trials may help elucidate the true benefit of hypofractionated high-dose-rate brachytherapy.

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)

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 Oncology
    Citation 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 Oncology
    Citation 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 Oncology
    Citation 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 Oncology
    Citation 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.

View all citing articles on Scopus
View full text