AUTHOR=Ong Ashley Li Kuan , Knight Kellie , Panettieri Vanessa , Dimmock Mathew , Tuan Jeffrey Kit Loong , Tan Hong Qi , Wright Caroline 

TITLE=Proton versus photon therapy for high-risk prostate cancer with dose escalation of dominant intraprostatic lesions: a preliminary planning study

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1241711

DOI=10.3389/fonc.2023.1241711

ISSN=2234-943X

ABSTRACT=<sec><title>Background and purpose</title><p>This study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (<italic>D</italic><sub>P</sub>) and accumulated dose (<italic>D</italic><sub>A</sub>) were utilized.</p></sec><sec><title>Materials and methods</title><p>In total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data.</p></sec><sec><title>Results</title><p>IMPT achieved a higher <italic>D</italic>mean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, <italic>p</italic> &lt; 0.05). Intermediate–high rectal and bladder doses were lower for IMPT (<italic>p</italic> &lt; 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, <italic>p</italic> &lt; 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, <italic>p</italic> &lt; 0.05). Rectal <italic>D</italic><sub>A</sub>-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (<italic>p</italic> &lt; 0.05). Bladder <italic>D</italic><sub>P</sub>-NTCP projected a higher GU toxicity than <italic>D</italic><sub>A</sub>-NTCP, with VMAT having the highest risk (<italic>p</italic> &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>Dose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate–high-dose range. The reduction in physical dose was translated into a lower NTCP (<italic>p</italic> &lt; 0.05) for the bladder, although rectal toxicity remained equivalent.</p></sec>