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Radiotherapy of prostate cancer with aspects on hypofractionation and high precision
Örebro University, School of Medical Sciences.
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hypofractionated radiotherapy (RT), including high dose rate brachy-therapy (HDR-BT) is a theoretically beneficial treatment option for curable prostate cancer. Our studies aimed to contribute to the growing body of results on the effectiveness and safety of HDR-BT both as monotherapy and as a boost in combination with external beam radiation therapy (EBRT).

In paper I, 229 patients (low- and intermediate-risk) received 2 – 4 fractions of HDR-BT as monotherapy. The median follow-up time was 85 months. In total, 9.6% had a biochemical failure (BF) and severe toxicities were uncommon. The treatment was found to be effective and safe.

In paper II, 355 patients (83% classified as high- or very high risk) received EBRT (3 Gy x 14) + a single fraction of HDR-BT (14.5 Gy). The median follow-up time was 56 months. The estimated five-year failure free survival was 79 % for the whole cohort. Our results suggest that this treatment appears to be feasible in terms of efficacy.

In paper III, 34 patients who received EBRT + HDR-BT were randomized to either five or three fractions of EBRT per week. Intrafractional prostate movement was tracked in real-time using the Raypilot® system. The primary endpoint was patient-reported acute toxicity. We found no significant difference between the study groups. Target displacement was less than 2 mm during 97% of the time, supporting the use of small treatment margins.

In paper IV, 175 patients received two fractions of HDR-BT (14 Gy x 2) as monotherapy. The estimated five-year cumulative BF rate was 3% for low-risk patients and 9.6% for intermediate-risk patients. The proportion of severe urinary and bowel toxicities were low, indicating that this treatment approach is effective and safe.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2025. , p. 73
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 309
Keywords [en]
Prostate cancer, radiation therapy, brachytherapy, high dose rate, hypofractionation
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-117125ISBN: 9789175296159 (print)ISBN: 9789175296166 (electronic)OAI: oai:DiVA.org:oru-117125DiVA, id: diva2:1909332
Public defence
2025-01-10, Örebro universitet, Campus USÖ, hörsal X1, Södra Grev Rosengatan 32, Örebro, 10:00 (Swedish)
Opponent
Supervisors
Available from: 2024-10-30 Created: 2024-10-30 Last updated: 2025-01-21Bibliographically approved
List of papers
1. High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center
Open this publication in new window or tab >>High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center
Show others...
2021 (English)In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 13, no 3, p. 245-253Article in journal (Refereed) Published
Abstract [en]

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), alpha/beta = 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.

Place, publisher, year, edition, pages
Termedia Publishing, 2021
Keywords
prostate cancer, HDR, brachytherapy, monotherapy, outcome
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-92355 (URN)10.5114/jcb.2021.105846 (DOI)000656311900002 ()34122563 (PubMedID)2-s2.0-85108190871 (Scopus ID)
Note

Funding Agency:

Örebro County Council  

Available from: 2021-06-14 Created: 2021-06-14 Last updated: 2025-01-21Bibliographically approved
2. Biochemical outcome of prostate cancer patients treated with hypofractionated external radiation and a single high-dose-rate brachytherapy boost
Open this publication in new window or tab >>Biochemical outcome of prostate cancer patients treated with hypofractionated external radiation and a single high-dose-rate brachytherapy boost
2025 (English)In: Brachytherapy, ISSN 1538-4721, E-ISSN 1873-1449, Vol. 24, no 1, p. 45-53Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Treating localized high-risk prostate cancer with a combination of external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) is a common approach. Moderately hypofractionated EBRT and a single HDR-BT boost simplifies the treatment. We aim to present our five-year results.

METHODS: In this study, 355 patients treated with moderately hypofractionated EBRT (42 Gy in 14 fractions) and a single HDR-BT boost (14.5 Gy) at Örebro University Hospital between 2008 and 2018 were included. They were followed with regular PSA tests.

RESULTS: The median age of the cohort was 70 years (range: 51-81) and the median follow-up duration was 56 months (range: 6-150). Among them, 45% were classified as very high-risk, 38% as high-risk and 17% as intermediate-risk. Adjuvant androgen deprivation therapy (ADT) with a median duration of 24 months was given to 75% of the patient cohort. The estimated 5-year failure free survival rates were 79% (whole cohort), 66% (very high-risk), 90% (high-risk) and 85% (intermediate-risk), respectively. Initial PSA > 10 ng/mL, Gleason score 9-10 and tumor stage T3 were significantly associated with biochemical failure (BF). A PSA bounce occurred in 53 (15%) cases and was inversely associated with BF (p = 0.001) for patients receiving ADT.

CONCLUSIONS: Moderately hypofractionated EBRT and a single HDR-BT boost seems to be an effective treatment against intermediate- and high-risk localized prostate cancer. Treatment escalation strategies should be investigated for very high-risk patients where the risk of recurrence remains high.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Boost, Bounce, Brachytherapy, HDR, Prostate cancer, Radiation therapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-117630 (URN)10.1016/j.brachy.2024.07.005 (DOI)001402302000001 ()39578204 (PubMedID)2-s2.0-85210092315 (Scopus ID)
Available from: 2024-12-09 Created: 2024-12-09 Last updated: 2025-01-31Bibliographically approved
3. A randomized trial on accelerated versus standard small-margin radiation schedule in patients with prostate cancer treated with combined brachytherapy and external beam radiation therapy: toxicity outcomes and patterns of prostate movement
Open this publication in new window or tab >>A randomized trial on accelerated versus standard small-margin radiation schedule in patients with prostate cancer treated with combined brachytherapy and external beam radiation therapy: toxicity outcomes and patterns of prostate movement
(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-117951 (URN)
Available from: 2024-12-27 Created: 2024-12-27 Last updated: 2024-12-27Bibliographically approved
4. Effectiveness, toxicity and impact on quality of life of high-dose-rate brachytherapy delivered in two fractions as monotherapy in patients with prostate cancer
Open this publication in new window or tab >>Effectiveness, toxicity and impact on quality of life of high-dose-rate brachytherapy delivered in two fractions as monotherapy in patients with prostate cancer
(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-117952 (URN)
Available from: 2024-12-27 Created: 2024-12-27 Last updated: 2024-12-27Bibliographically approved

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