Henrike Westerveld

Prospective evaluation of AI-based BiCycle autoplanning for advanced cervical cancer brachytherapy

Rule-based AI BiCycle autoplanning compared favorably with manual planning in retrospective planning studies. In this study, we prospectively evaluated BiCycle's 'real life' impact by running it in parallel to current manual planning. Apart from dosimetric evaluations, treating physicians scored plans, and planning times were recorded. Following clinical routine, in each brachytherapy fraction, an RTT manually generated a plan which was then optionally adjusted by the treating physician, yielding the Man_Adj plan that was delivered. After treatment, a plan was automatically generated using BiCycle, followed by optional adjustment by the treating physician in the clinical TPS (Auto_Adj plan). Man_Adj and Auto_Adj plans were mutually compared and all planning time recorded. Physicians scored plan quality differences. For 28 of 37 evaluated fractions, the treating physician scored a higher quality for the Auto_Adj plan, in 7 fractions there was parity, and for 2 fractions Man_Adj was preferred. With comparable CTV For 95% of fractions, the treatment plan based on autoplanning was either preferred by the involved physician (76% of fractions) or considered similar in quality as the clinical plan (19%). Planning time reduced from 44.1 min for the manual workflow to 9.4 min. The system has recently been clinically introduced, following with the EU Medical Device Regulation.

Impact of primary radiotherapy on the psychosocial well-being of patients with locally advanced cervical cancer (IMPRaCC study)

Treatment for locally advanced cervical cancer (LACC), and especially brachytherapy, can be physically and psychologically demanding for patients. The IMPRaCC study (Impact of primary Radiotherapy on the psychosocial well-being of patients with LACC) aimed to investigate risk factors, peak moments of distress, and unmet needs. Analyses of EORTC-C30 questionnaires in a cohort of LACC patients (2019-2024) were combined with semi-structured interviews 4-16 weeks post-treatment. Questionnaires were collected at baseline, during treatment, and regularly throughout follow-up up to two years. Linear-mixed models evaluated changes in scores from baseline. Scores were also compared to a healthy reference population. Logistic regression identified factors associated with deteriorations in emotional (EF) and social functioning (SF) and fatigue during treatment and follow-ups. Interviews were evaluated using thematic analyses. Among 142 LACC patients, baseline EF and SF during treatment were impaired compared to the reference population, but improved in follow-up. Deteriorations in EF, SF and fatigue were more frequent during treatment (18.6%, 48.8%, 62.8%) than follow-up (10.4%, 25%, 34.4%). Psychiatric history was associated with worse SF during treatment, while being in a relationship and psychological support were protective factors. Brachytherapy delivered in four vs. three fractions seemed to be associated with worse EF, SF and fatigue. Interviews with 13 patients revealed emotional distress, especially before brachytherapy, and need for clear and consistent communication across multiple healthcare professionals. Psychiatric history assessments, psychological support, and consistent communication support tailored care for LACC patients. Brachytherapy regimens of three fractions may further reduce psychosocial distress.

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.

Cost-utility-analysis of molecular-integrated-profile for women with (high)intermediate risk endometrial cancer - PORTEC-4a an international, randomised, phase 3 trial.

The international PORTEC-4a trial demonstrated that individualised adjuvant treatment for women with (high)intermediate risk endometrial cancer (HIR-EC), guided by a molecular-integrated-risk-profile, achieves similar high local tumour control, while nearly half of patients were spared adjuvant treatment. Although determination of the molecular-integrated-profile increases diagnostics costs due to additional immunohistochemistry and DNA-sequencing, these costs may be offset by savings on other care and improved patient outcomes. Women with early-stage HIR-EC eligible for the PORTEC-4a trial, were randomised (2:1) to either adjuvant treatment according to their molecular-integrated-profile or standard vaginal brachytherapy (VBT). EC-related costs were evaluated from a healthcare perspective over a three-year follow-up period. Costs were related to quality-adjusted-life-years (QALYs) using the EORTC-QLU-C10D instrument. T-test compared mean QALYs and costs, with multiple imputation for missing data. All 564 patients were included in the cost-utility-analysis; 367 in molecular-profile arm and 197 in standard arm. QALYs were comparable (p = 0.58). Total healthcare costs were somewhat, but not significantly, lower in molecular-profile arm compared to standard arm (€11,898 vs €13,047, p = 0.11). Costs spent up until recurrence were significantly lower in molecular-profile arm (€9,995 vs €11,926, p < 0.01), while there was no significant difference in treatment for recurrence (€1,903 vs €1,121, p = 0.17). At a willingness-to-pay threshold of €20,000/QALY, the strategy as proposed by PORTEC-4a was 89% likely to be cost-effective. Individualised adjuvant treatment based on a molecular-integrated-profile was more cost-effective than standard VBT for patients with HIR-EC. These results further support the implementation of the molecular-integrated-profile in routine clinical practice.