Dataset Information

Determining the safety of ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: A toxicity assessment of 150 patients.

ABSTRACT:

Background and purpose

Local re-treatment of radiorecurrent prostate cancer is potentially curative. However, the increased risk of severe toxicity may outweigh the opportunity of cancer control. This study aims to evaluate treatment-related toxicity from ultrafocal salvage high-dose-rate brachytherapy (HDR-BT) and to investigate potential risk factors.

Materials and methods

Toxicity data from 150 treated patients (July 2013-November 2019) was collected from a prospective registry. The treatment aim was to deliver a single dose of 19 Gy to the recurrent lesion as identified on multiparametric MRI and PET-CT. Treating physicians graded genitourinary (GU) and gastro-intestinal (GI) toxicity and erectile dysfunction (ED) using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0, at baseline and during follow-up. Domains with substantial (?10%) new-onset grade ? 2 toxicity were further evaluated using mixed effects logistic regression to find potential risk factors.

Results

Median follow-up time was 20 months (IQR 12-31). Over time, new-onset grade 2 and 3 toxicity was recorded in 41% and 3% (GU), 5% and 0% (GI) and 22% and 15% (ED). While GI toxicity remained stably low, grade ? 2 GU toxicity and ED were seen twice as frequent in the late phase (>3 months after treatment). Significant risk factors for grade ? 2 toxicity were baseline GU toxicity (grade ? 2), baseline ED (grade ? 2), IPSS (cut-off ? 14) and urethral dose (D10%, cut-off ? 17 Gy).

Conclusion

Ultrafocal salvage HDR-BT is a safe re-treatment option, especially in patients with a favorable symptom profile at baseline. Adherence to urethral dose constraints is important to avoid GU toxicity.

SUBMITTER: van Son M

PROVIDER: S-EPMC7750686 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Determining the safety of ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: A toxicity assessment of 150 patients.

van Son Marieke M Peters Max M Moerland Marinus M van de Pol Sandrine S Eppinga Wietse W Lagendijk Jan J van der Voort van Zyp Jochem J

Clinical and translational radiation oncology 20201211

<h4>Background and purpose</h4>Local re-treatment of radiorecurrent prostate cancer is potentially curative. However, the increased risk of severe toxicity may outweigh the opportunity of cancer control. This study aims to evaluate treatment-related toxicity from ultrafocal salvage high-dose-rate brachytherapy (HDR-BT) and to investigate potential risk factors.<h4>Materials and methods</h4>Toxicity data from 150 treated patients (July 2013-November 2019) was collected from a prospective registry ...[more]

PMID: 33364450

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Project description:PurposeNCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response.Methods and materialsThis trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter.ResultsBetween August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment.ConclusionsThe MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.

Project description:To compare the outcomes of localized prostate cancer treatment with high-dose-rate brachytherapy (HDR-BT) and low-dose-rate brachytherapy (LDR-BT), we examined 924 patients treated with HDR-BT + external beam radiotherapy (EBRT) and 500 patients treated with LDR-BT ± EBRT using multi-institutional retrospective data. The HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. To reduce background selection bias, we performed inverse probability of treatment weighting (IPTW) analysis using propensity scores and excluded patients with T3b-4 disease/ initial prostate-specific antigen (PSA) levels > 50 ng/ml. The actuarial 5-year biochemical control rates (5y-bNED) were 96.3% and 95.7% in the HDR-BT and LDR-BT groups, respectively. The corresponding values were 100% and 96.5% in the low-risk group; 97.4% and 97.1% in the intermediate-risk group (97.2% and 97% in the higher titer group and 97.5% and 94.6% in the lower titer group, respectively); and 95.7% and 94.9% in the selected high-risk group, respectively. IPTW correction indicated no significant difference among the groups. The 5y-bNED in the HDR-BT + EBRT, LDR-BT + EBRT, and LDR-BT alone groups were 96.3%, 95.5%, and 97%, respectively (P = 0.3011). The corresponding values were 97.4%, 94.7%, and 96.6% (P = 0.1004) in the intermediate-risk group (97.5%, 100%, and 94.5% in the lower titer group [P = 0.122] and 97.2%, 96.2%, and 100% [P = 0.664] in the higher titer group, respectively) and 95.7%, 95.5%, and 100% (P = 0.859) in the high-risk group, respectively. The HDR-BT group showed a lower incidence of acute grade ≥ 2 genitourinary toxicities; the incidence of other early and late grade ≥ 2 toxicities were similar between the HDR-BT and LDR-BT groups. Acute genitourinary toxicity predicted the occurrence of late genitourinary toxicity. EBRT increased the risk of grade ≥ 2 gastrointestinal toxicity. HDR-BT + EBRT is a good alternative to LDR-BT ± EBRT for low-, intermediate-, and selected high-risk patients.

Project description:PurposeBi-objective simultaneous optimization of catheter positions and dwell times for high-dose-rate (HDR) prostate brachytherapy, based directly on dose-volume indices, has shown promising results. However, optimization with the state-of-the-art evolutionary algorithm MO-RV-GOMEA so far required several hours of runtime, and resulting catheter positions were not always clinically feasible. The aim of this study is to extend the optimization model and apply GPU parallelization to achieve clinically acceptable computation times. The resulting optimization procedure is compared with a previously introduced method based solely on geometric criteria, the adapted Centroidal Voronoi Tessellations (CVT) algorithm.MethodsBi-objective simultaneous optimization was performed with a GPU-parallelized version of MO-RV-GOMEA. This optimization of catheter positions and dwell times was retrospectively applied to the data of 26 patients previously treated with HDR prostate brachytherapy for 8-16 catheters (steps of 2). Optimization of catheter positions using CVT was performed in seconds, after which optimization of only the dwell times using MO-RV-GOMEA was performed in 1 min.ResultsSimultaneous optimization of catheter positions and dwell times using MO-RV-GOMEA was performed in 5 min. For 16 down to 8 catheters (steps of 2), MO-RV-GOMEA found plans satisfying the planning-aims for 20, 20, 18, 14, and 11 out of the 26 patients, respectively. CVT achieved this for 19, 17, 13, 9, and 2 patients, respectively. The P-value for the difference between MO-RV-GOMEA and CVT was 0.023 for 16 catheters, 0.005 for 14 catheters, and <0.001 for 12, 10, and 8 catheters.ConclusionsWith bi-objective simultaneous optimization on a GPU, high-quality catheter positions can now be obtained within 5 min, which is clinically acceptable, but slower than CVT. For 16 catheters, the difference between MO-RV-GOMEA and CVT is clinically irrelevant. For 14 catheters and less, MO-RV-GOMEA outperforms CVT in finding plans satisfying all planning-aims.

Dataset Information

Determining the safety of ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: A toxicity assessment of 150 patients.

Background and purpose

Materials and methods

Results

Conclusion

Publications

Determining the safety of ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: A toxicity assessment of 150 patients.

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