Mischa S Hoogeman

Margin and robustness settings for a library-of-plans IMPT strategy for locally advanced cervical cancer

Abstract Objective. This study aims to determine a margin and robustness setting for treating locally advanced cervical cancer (LACC) with a library-of-plans (LoP) based online-adaptive intensity-modulated proton therapy (IMPT). Approach. We analyzed 13 LACC patients with delineated planning and weekly repeat CT scans (reCTs). For each patient, 120 IMPT treatments of 25 fractions were simulated with a LoPs approach. Six different robustness settings (2–7 mm set-up robustness (SR) plus 3% range robustness (RR)) were used to create those 120 IMPT plans. Each fraction was simulated with a weekly reCT, combined with the sampling of inter- and intrafraction treatment uncertainties. The fraction doses were accumulated to obtain a treatment dose to the target volumes, distinguishing between the low-risk clinical target volume (CTV-T-LR) and the elective CTV (CTV-E). If one of the two targets obtained an adequate coverage for more than 90% of the treatments, different anisotropic margins were sampled on top of the robustness setting to the other target to obtain the Pareto-optimal margin in terms of adequate coverage versus increase in target volume. Main results. The percentage of treatments that reach the dose criterion V 42.75Gy > 95% for the CTV-T-LR was 22.3%, 28.5%, 51.2%, 73.1%, 85.3%, and 90.0% for 2, 3, 4, 5, 6, and 7 mm SR plus 3% RR and for the CTV-E, this percentage was 60.4%, 73.8%, 86.5%, 92.3%, 96.9%, and 98.5%. The Pareto-optimal margin combined with a 5 mm/3% robustness setting for the CTV-T-LR with an adequate coverage for >90% of the treatments was given by {0, 1, 0, 3, 3, 0} mm in the left, right, anterior, posterior, cranial, caudal direction. Significance. Our study evaluated combinations of robustness and anisotropic margin settings for IMPT for LACC. With 5 mm SR and 3% RR for CTV-E and CTV-T-LR plus a margin to the CTV-T-LR of {0, 1, 0, 3, 3, 0} mm in left, right, anterior, posterior, cranial, and caudal ensured an adequate coverage for >90% of the simulated IMPT treatments.

Afterloader integrated EMT enables improved dwell position model definition and quality assurance in Venezia gynaecological brachytherapy applicators

Abstract Objective. In brachytherapy for gynecological cancers using intracavitary applicators, implant reconstruction is commonly performed using applicator libraries. These libraries contain applicator geometry models as well as dwell position (DP) models defined in respect to the applicator geometry. In this study, we investigate whether an afterloader integrated electromagnetic tracking (EMT) system can be utilized for DP model definition and quality assurance in such applicators. Approach. DPs in four sets of two configurations of the Elekta Venezia Advanced Gynaecological Applicator (22 mm ovoids/40 mm intrauterine (IU) and 26 mm ovoids/70 mm IU) were measured using an afterloader integrated EMT system. Measurements were evaluated for reproducibility and compared against manufacturer-specified (MS) DPs and a computed tomography (CT)-corrected DP model. Main Results. Excellent EMT measurement reproducibility was observed, with values of ⩽0.2 mm for both configurations. The overall reproducibility, including applicator geometry reproducibility, was ⩽0.4 mm for both configurations. Significant discrepancies from the manufacturer’s DP model were observed, with a mean ± sd deviation of 1.13 ± 0.66 mm (22/40) and 1.37 ± 0.63 (26/70), particularly in the IU channel, where MS DPs were not experimentally defined. Discrepancies were reduced to 0.89 ± 0.41 mm (22/40) and 0.81 ± 0.33 mm (26/70) when the CT-corrected DP model was used as baseline, highlighting the need for experimentally defined DP models. The overall uncertainty of single measurements was below the clinically acceptable 2 mm limit. Significance. This study confirms that afterloader integrated EMT can accurately reconstruct source paths in gynecological brachytherapy applicators and supports its incorporation into clinical workflows for improved quality assurance and treatment precision. The importance of EMT for quality assurance was highlighted by measured deviations from manufacturer’s DP model in a clinical relevant part of the IU channel.

Changes in bone marrow fat fraction and immune cell counts in women with cervical cancer treated with primary chemoradiotherapy

Hematologic toxicity (HT) is a common effect of chemoradiotherapy in primary locally advanced cervical cancer (LACC) and related to bone marrow (BM) fat increase. However, longitudinal effects and dose-relationships are unknown. In this study, pre- and post-treatment BM fat fraction and blood immune cell counts were evaluated in women with primary LACC undergoing BM sparing chemoradiotherapy. Water-fat MRI scans and blood samples were obtained at baseline, during, and at 3 and 12 months (post-)treatment. The mean proton density fat fraction (PDFF) [%] was calculated for each vertebra, categorized into a no (5 Gy) dose group, and the pelvic bones. Associations between PDFF and dose, immune cells, and patient characteristics were assessed with linear mixed models. Eighteen women were included. Vertebral PDFF in the no dose group remained unchanged, whereas the low and high dose group showed an increase of 24-35 PDFF% during treatment. PDFF in the low dose group recovered slightly but remained elevated up to 12 months post-treatment. Mean dose to pelvic subregions was ≥ 18.8 Gy and PDFF increase was 12-29 PDFF%. Only the lower pelvic PDFF recovered to baseline. Blood immune cell decline lasted up to 12 months post-treatment and was correlated with higher mean vertebral PDFF. Vertebral fat fraction increased during treatment for dose > 1 Gy, without post-treatment recovery for dose > 5 Gy. Immunosuppression persisted up to 12 months post-treatment and was related to a higher mean vertebral PDFF. 5 Gy might be relevant for BM damage, but this threshold should be validated.