Optimising External Beam Radiotherapy for Prostate Cancer. Advances in Treatment Planning
Author
Summary, in English
Background
Radiotherapy (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.
Aims
This 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).
Methods
A 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).
Results
Paper 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.
Conclusions
To 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.
Radiotherapy (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.
Aims
This 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).
Methods
A 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).
Results
Paper 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.
Conclusions
To 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.
Department/s
Publishing year
2024
Language
English
Publication/Series
Lund University, Faculty of Medicine Doctoral Dissertation Series
Issue
2024:50
Full text
Document type
Dissertation
Publisher
Lund University, Faculty of Medicine
Topic
- Radiology, Nuclear Medicine and Medical Imaging
Status
Published
Supervisor
- Adalsteinn Gunnlaugsson
- Elinore Wieslander
- Sven Bäck
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-8021-543-5
Defence date
19 April 2024
Defence time
09:00
Defence place
Onkologiklinikens föreläsningssal, Klinikgatan 5, plan 3, Universitetssjukhuset i Lund
Opponent
- Niclas Pettersson (docent)