Adaptive sequential plan-on-plan optimization during prostate-specific antigen response guided radiotherapy of recurrent prostate cancer

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 68 Gallium-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.

A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and 68Ga-PSMA-PET for biochemical relapse after radical prostatectomy – The PROPER 1 trial

“…Another unique factor in our study is the sequential plan-on-plan VMAT optimisation method that we developed to adapt the SRT according to PSA response. When implementing new radiotherapy techniques, it is important to verify their robustness with thorough QA procedures (as reported previously [14]) and to prospectively study the clinical feasibility, as described in the present paper.…”

“…The adaptive sequential radiotherapy treatment techniques used in PROPER I trial have been described in detail previously [14]. Initially, all patients were prescribed 70 Gy to the prostate bed in 35 fractions.…”

“…All target volumes were treated with 1 fraction/day and 5 fractions/week. To be able to adapt the SRT for non-responders, and to add LNI and boost doses during SRT, we developed the biologically adaptive plan-on-plan volumetric-modulated-arc-therapy method, which has been described elsewhere [14].…”

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

“…Thirty-four (35 %) were classified as responders, and 63 (65 %) as non-responders. The median follow-up time was 38 months (IQR 29–48) [21] .…”

“…All patients in the PROPER I trial were treated with volumetric modulated arc therapy (VMAT), and the treatment planning was carried out in Eclipse versions 13.6 and 15.6 (Varian Medical Systems, Palo Alto, CA, USA) with the anisotropic analytical algorithm versions 10.0.28 and 13.6.23. The adaptation for non-responders to include pelvic lymph nodes was made with a sequential plan-on-plan VMAT technique, which has been previously reported [21] . Dose volume objectives from the PROPER I trial are presented in Supplementary Table 1 .…”