A radiobiological study of the schemes with a low number of fractions in high-dose-rate brachytherapy as monotherapy for prostate cancer

Guirado, D.; Ruiz-Arrebola, S.; Tornero-López, A.; Vega, José M.; Prada, Pedro J.; Lallena, A. M.

doi:10.5114/jcb.2020.94492

Cited by 3 publications

(5 citation statements)

References 38 publications

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“…The acute urethral grade 2-3 toxicity of 24% compares well to the large Offenbach series, with 20-25% of grade 2-3 reactions [19]. Only 3% of patients had a temporary catheterization, which was less then reported from LDR seed brachytherapy series [27]. When considering late LUTS effects, we found no or minor impairments.…”

Section: Discussionsupporting

confidence: 67%

“…Prostate specific antigen regression between the different fractionation cohorts was nearly identical, supporting a low α/β ratio of 3. In a recent radiobiological study, based on overview data from clinical studies with few and high doses per fraction, the calculated α/β ratio was surprisingly 22.8 Gy, suggesting that the value was uncertain with high and few fractions [27]. In contrast, other published calculations of α/β ratio showed a low value of 1.4 [7].…”

Section: Discussionmentioning

confidence: 97%

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High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center

Johansson¹,

Olsén²,

Karlsson

et al. 2021

jcb

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Purpose: Until now, most long-term results for brachytherapy only has been published for low-dose-rate (LDR) seeds. Due to radiobiology reasons, high-dose-rate (HDR) mono-brachytherapy is of growing interest. The aim of the study was to report long-term biochemical control rate and toxicities with HDR monotherapy.Material and methods: This was a retrospective single-institution experience, including 229 men, clinically staged T1c-T2b, Gleason 3 + 3 (prostate specific antigen (PSA) ≤ 15), or Gleason 3 + 4 (PSA ≤ 10), consecutively treated between 2004 and 2012 with HDR brachytherapy alone, using three different fractionation schedules of 92-95 Gy (EQD(2), α/β = 3). Group 4F (n = 19) had a single implant of 9.5 Gy in four fractions over 2 days. Group 3F (n = 107) had three separate implants of 11 Gy over 4 weeks. Group 2F (n = 103) had two implants of 14 Gy over 2 weeks. No adjuvant hormonal therapy was allowed.Results: For 4F, 3F, and 2F study groups, median follow-up was 10.2, 7.1, and 6.1 years, respectively, and biochemical failure rate was 10.5%, 4.7%, and 14.6%, respectively. Early and late side effects were followed with common terminology criteria version 2.0 and patient-reported questionnaires. There were a temporary acute urethral toxicity increase, 1-2 grades over baseline lower urinary tract symptoms (LUTS), which usually recovered. About 1/3 of the patients had a remaining one grade over baseline LUTS. Severe grade 3-4 toxicity were only found in 3.5% of patients. No rectal toxicity was observed. Erectile dysfunction (ED) was depending on age and erectile function before treatment. In patients without ED before the treatment, we found a complete ED in 21% of men at the last follow-up.Conclusions: In the present study, HDR mono-brachytherapy was found to be an effective treatment, with mild long-term side effects difficult to differentiate from aging effects. There were no significant differences in PSA regression, PSA failure rate, and toxicity between the different fraction schedules.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 97%

High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center

Johansson¹,

Olsén²,

Karlsson

et al. 2021

jcb

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“…We used an in-house developed algorithm The space of parameter values was constrained to avoid reaching solutions that could be unphysical or not supported by biological data, and to speed up convergence. In particular, dose compensation due to accelerated proliferation was limited to λ' ≤ 2 Gy day -1 , a limit well higher than the proliferation found in [14], and the half-life of sublethal repair was limited to T repair ≤ 6 h. For the α/β ratio, we employed two different constraints due to the discrepancies on the reported values from external radiotherapy and HDR-BT: on the one hand, a constraint 1 ≤ α/β ≤ 100 Gy to allow for large α/β ratios like those reported in [15]; on the other hand, a stronger constraint 1 ≤ α/β ≤ 8…”

Section: Methodsmentioning

confidence: 99%

“…This loss in tumor control is not supported by a low α/β ratio. Guirado et al have recently analyzed the response of prostate cancer to HDR-BT, suggesting a large α/β ratio (~23 Gy) to explain the poor control achieved with HDR-BT single-fraction treatments [15]. They also argued that the linear-quadratic (LQ) model may not be adequate to describe the response to very large doses per fraction.…”

Section: Introductionmentioning

confidence: 99%

Radiobiological meta-analysis of the response of prostate cancer to high dose rate brachytherapy

Kölmel,

Pombar,

Pardo-Montero

2024

Preprint

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Background and purposeClinical studies have shown a marked reduction in tumor control in prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT). The purpose of this study was to analyze the dose-response of prostate cancer treated with HDR-BT, specifically aiming at investigating the potential failure of the linear-quadratic (LQ) model to describe the response at large dosesper-fraction.Materials and methodsWe collated a dataset of dose-response to HDR-BT (3258 patients). The analysis was conducted separately for low and intermediate risk, resulting in 21 schedules (1643 patients) and 22 schedules (1615 patients), respectively. Data were fitted to tumor control probability models based on the LQ model, the linear-quadratic-linear (LQL), and a modification of the LQ model to include the effect of reoxygenation during treatment.ResultsThe LQ cannot fit the data unless the α/β is allowed to be very high (∼[20-100] Gy, 95% confidence interval). If the α/β is constrained to be low (< 8 Gy) the LQ model cannot reproduce the clinical results, and the LQL model, which includes a moderation of radiation damage with increasing dose, significantly improves the fitting. On the other hand, the reoxygenation model does not match the results obtained with the LQL.ConclusionThe clinically observed reduction in tumor control in prostate cancer treated with radical HDR-BT is better described by the LQL model. Using the best-fitting parameters, the BED for a 20 Gy × 1 treatment (95 Gy) is far less than that of a conventional 2 Gy × 37 fractionation (184 Gy). These results may assist in the design of radical HDR-BT treatment.

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“…Several studies have demonstrated favorable toxicity rates and excellent results in the impact on quality of life after 19 Gy single-fraction high-dose-rate brachytherapy (HDR-BT 19 Gy) [ 1 , 2 , 3 , 4 , 5 ]. However, in the last few years, some trials have reported higher biochemical and local failure rates than expected with this dose schedule [ 5 , 6 , 7 , 8 , 9 ].…”

Section: Purposementioning

confidence: 99%

Salvage brachytherapy for locally recurrent prostate cancer after single-fraction 19 Gy high-dose-rate brachytherapy: toxicity, prostate-specific antigen kinetics, and cancer control

Mayrata¹,

Espinosa²,

Büchser³

et al. 2021

jcb

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Purpose To evaluate toxicity, prostate-specific antigen (PSA) kinetics, and cancer control of high-dose-rate brachytherapy (HDR-BT) as a salvage modality for men with locally recurrent prostate cancer, after primary HDR-BT failure. Material and methods Twelve patients with biochemical failure and a local relapse after 19 Gy single-fraction high-dose-rate brachytherapy (HDR-BT 19 Gy) were salvaged using two HDR-BT fractions. Salvage treatment consisted of two HDR-BT applications, one week apart, delivering 12 Gy to the prostate per application (HDR-BT 12 × 2). Results Median age and initial PSA prior to rescue treatment were 74 years (range, 65-80) and 5.29 ng/ml (range, 2.37-16.40), respectively. Forty-two percent had a low-risk and 58% presented with intermediate-risk prostate cancer. Median follow-up period was 26 months (range, 10-42). Median time to PSA nadir was 12 months, with a median value of 0.21 ng/ml. Most of the patients (11 of 12) achieved a PSA decline ≥ 90%. Acute grade 2 genitourinary (GU) toxicity occurred in 4 patients (33.3%) and none presented with acute gastrointestinal (GI) toxicity. Two patients (16.7%) suffered from late GU grade 2 toxicity. No grade 3 toxicity were recorded. To date, 2 patients (16.7%) have experienced biochemical failure after salvage treatment. Conclusions Salvage HDR-BT 12 × 2 is a feasible and well-tolerated treatment, with acceptable toxicity rates for men with locally recurrent prostate cancer, who failed after HDR-BT with 19 Gy. Moreover, PSA kinetics and cancer control after salvage treatment suggest that this strategy might be efficacious in this clinical setting.

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A radiobiological study of the schemes with a low number of fractions in high-dose-rate brachytherapy as monotherapy for prostate cancer

Cited by 3 publications

References 38 publications

High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center

High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center

Radiobiological meta-analysis of the response of prostate cancer to high dose rate brachytherapy

Salvage brachytherapy for locally recurrent prostate cancer after single-fraction 19 Gy high-dose-rate brachytherapy: toxicity, prostate-specific antigen kinetics, and cancer control

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