| 1. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and Ga-68-PSMA-PET for biochemical relapse after radical prostatectomy-The PROPER 1 trial
- 2022
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 36, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still >= 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.
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| 2. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome – 5 year follow-up of a prospective observational study
- 2020
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 24, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome.Materials and methods: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression.Results: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses.Conclusion: The addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.
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| 3. |
- Jóhannesson, Vilberg, et al.
(författare)
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Adaptive sequential plan-on-plan optimization during prostate-specific antigen response guided radiotherapy of recurrent prostate cancer
- 2021
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 18, s. 5-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment adaptation based on tumour biomarker response during radiotherapy of prostate cancer, could be used for both escalation and de-escalation of radiation doses and volumes. To execute an adaptation involving extension of treatment volumes during radiation can however be restricted by the doses already delivered. The aim of this work was to develop a treatment planning method that addresses this challenge. Material and methods: A volumetric-modulated-arc-therapy (VMAT) planning method with sequential plan-on-plan optimization was developed for a prospective phase II trial including 100 patients on salvage radiotherapy (SRT) for prostate cancer recurrence. A treatment adaptation was performed after five weeks of SRT based on prostate-specific antigen response during this phase of the treatment. This involved extension of treatment volumes for non-responders (n = 64) to include pelvic lymph nodes and boost to 68Gallium-Prostate-Specific-Membrane-Antigen-Positron-Emission-Tomography positive lesions. This method was evolved by introducing an EQD2 (equivalent dose in 2.0 Gy fractions) correction of the base plan for improved dose coverage. Results: All dose-volume criteria for target coverage were met for the non-responders when based on physical dose. An EQD2 correction of the base plan for non-responders, implemented for the final 29 patients, led to a statistically significant improvement in dose coverage as compared to the 35 patients treated without EQD2 correction. Conclusions: This is to our knowledge the only study presented on biomarker-guided sequential VMAT radiotherapy using a plan-on-plan technique in the pelvis. By using a biologically adapted technique an improved target coverage was achieved without compromising doses to organs at risk.
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| 4. |
- Jóhannesson, Vilberg, et al.
(författare)
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Dose-volume relationships of planned versus estimated delivered radiation doses to pelvic organs at risk and side effects in patients treated with salvage radiotherapy for recurrent prostate cancer
- 2024
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Ingår i: Technical Innovations and Patient Support in Radiation Oncology. - 2405-6324. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate estimated delivered dose distributions using weekly cone-beam computed tomography (CBCT) scans for pelvic organs at risk (OARs) in salvage radiotherapy (SRT) after radical prostatectomy. Furthermore, to compare them with the originally planned dose distributions and analyse associations with gastrointestinal (GI) and genitourinary (GU) side effects.METHODS: This study is part of a phase II trial involving SRT for recurrent prostate cancer. Treatment was personalised based on PSA response during SRT, classifying patients as PSA responders or non-responders. Estimated radiation dose distributions were obtained using deformable image registration from weekly CBCT scans. GI and GU toxicities were assessed using the RTOG toxicity scale, while patient-reported symptoms were monitored through self-assessment questionnaires.RESULTS: The study included 100 patients, with similar treatment-related side effects observed in both responders and non-responders. Differences in dose-volume metrics between the planned and estimated delivered doses for the examined OARs were mostly modest, although generally statistically significant. We identified statistically significant associations between QUANTEC-recommended dose-volume constraints and acute bowel toxicity, as well as late urinary patient-reported symptoms, for both the estimated delivered and planned dose distributions.CONCLUSION: We found small but statistically significant differences between estimated delivered and planned doses to OARs. These differences showed trends toward improved associations for estimated delivered dose distributions with side effects. Enhanced registration methods and imaging techniques could potentially further enhance the assessment of truly delivered doses and yield more reliable dose-volume constraints for future therapies.
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| 5. |
- Jóhannesson, Vilberg
(författare)
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Optimising External Beam Radiotherapy for Prostate Cancer. Advances in Treatment Planning
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundRadiotherapy (RT) is an effective treatment option for prostate cancer (PCa). The evolution of new treatment planning techniques, advanced imaging and accelerator design has enabled precise treatment delivery. Volumetric modulated arc therapy (VMAT) optimisation techniques achieve sharp dose gradients between the target and organs at risk (OAR) and have become the standard of care for PCa RT. AimsThis project aimed to enhance and develop advanced radiation planning techniques for optimising VMAT for primary and recurrent prostate cancer. Additionally, we explored new adaptive radiation therapy approaches based on tumour biomarker response during the initial part of the RT for patients with recurrent disease (Papers I-II). The aims of the work in Paper III were to use image registration to compare the planned radiation doses with the estimated delivered doses. Additionally, the study aimed to examine their relation to side effects. Furthermore, we assessed the feasibility of using the simultaneous integrated boost (SIB) VMAT technique for planning ultra-hypofractionated (UHF) RT in patients with targets including both the prostate and seminal vesicles (SV) (Paper IV).MethodsA new treatment-planning concept was developed, including corrections for fractionation effects (EQD2α/β=3-dose conversions) with the so-called plan-on-plan technique in a prospective phase II trial (PROPER 1). The study included patients with biochemical recurrence after radical prostatectomy (RP), and all patients received RT to the prostate bed. Patients who did not have a prostate-specific antigen (PSA) response according to the study protocol during the first five weeks of RT were to receive additional treatment to regional lymph nodes (Papers I-II). Cone-beam computed tomography (CBCT) imaging data from the PROPER 1 study was used to analyse estimated delivered radiation dose distributions, comparing them with initial plans (Paper III) and evaluating potential dose-volume associations with side effects. In Paper IV, treatment structures have been redefined for patients within the HYPO-RT-PC trial, and we have estimated the feasibility of SIB techniques to include SV in the target volume with UHF fractionation compared with conventional fractionation (CF).ResultsPaper I: An EQD2 fractionation correction of the plan-on-plan for non-responding patients in PROPER 1 improved target dose coverage.Paper II: The three-year failure-free survival was 94% for responders and 68% for non-responders, which compared favourably to historical controls. The study treatment was well tolerated. Paper III: We have observed small but statistically significant differences between the planned and estimated delivered doses to OARs. These differences indicate improved associations between estimated delivered dose distributions and side effects.Paper IV: UHF RT, based on the HYPO-RT-PC trial fractionation schedule, with a SIB technique to the prostate and the base of the SV, can be planned with generally lower doses to OARs.ConclusionsTo our knowledge, PROPER 1 is the only study presented on biomarker-guided sequential VMAT radiotherapy using a fractionation-corrected adapted plan-on-plan technique in the pelvis. This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results have laid the foundation for the prospective randomised trial, PROPER 2 (NCT04858880).Applying a SIB technique for treating both the prostate and the base of the seminal vesicles with UHF RT (based on the HYPO-RT-PC fractionation schedule) resulted in lower EQD2-corrected doses to organs at risk compared to conventionally fractionated radiotherapy delivered with sequential boost technique.
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