Eva Meixner

Background/Objectives: Proton therapy is widely used in paediatric neuro-oncology because of its favourable dose distribution and reduced exposure to radiation of healthy tissue. Nevertheless, current knowledge regarding radiation-induced contrast enhancements (RICE) is largely derived from adult proton therapy cohorts, while evidence in paediatric patients remains limited and the underlying biological mechanisms are still incompletely understood. This study investigated the incidence of RICE in paediatric patients with low-grade glioma (LGG) and ependymoma and evaluated potential associations with linear energy transfer (LET) and variable relative biological effectiveness (RBE)-weighted dose distributions. Methods: In this retrospective single-centre study, paediatric patients with LGG or ependymoma were identified from a prospectively maintained institutional registry patients treated with proton therapy at the Heidelberg Ion-Beam Therapy Centre (HIT) between 2010 and 2024. Follow-up magnetic resonance imaging examinations were systematically reviewed for RICE. Lesions were contoured in RayStation and assessed dosimetrically using a fixed RBE of 1.1 and three variable RBE models. LET-weighted dose metrics and Dose_(RBE) × LET products were compared between RICE regions and planning target volumes (PTVs). Overall survival and progression-free survival were estimated using Kaplan–Meier method. Results: Seventy-six patients met the inclusion criteria, including 33 patients with LGG and 43 with ependymoma. A total of 724 follow-up magnetic resonance imaging examinations were reviewed. RICE occurred in six patients (7.9%), exclusively in the ependymoma subgroup (14.0%). Higher prescribed radiation dose was significantly associated with RICE occurrence (p = 0.031). Across all variable RBE models, biologically weighted dose estimates and Dose_(RBE) × LET products were consistently elevated within RICE regions compared with corresponding PTV regions, particularly at low- and intermediate-dose levels. Five-year overall survival rates were 91.7% for LGG and 86.6% for ependymoma, while corresponding progression-free survival rates were 84.4% and 69.3%, respectively. Conclusions: Variable RBE models identified biologically relevant dose heterogeneities within RICE regions that were not adequately captured by the conventional fixed RBE approach. These findings suggest that LET-associated biological dose escalation may contribute to radiation-related brain tissue changes after proton therapy and support further investigation and prospective validation of LET- and RBE-informed normal-tissue risk assessment in paediatric neuro-oncology.

Background: Deep inspiration breath-hold (DIBH) is a radiotherapy standard technique for cardiac-sparing in breast cancer, particularly for left-sided tumors. However, not all patients can successfully complete DIBH RT in clinical routine, necessitating conversion to free breathing (FB) techniques and replanning. This study aimed to identify clinical factors predictive of DIBH feasibility to optimize patient selection and resource utilization. Methods: This retrospective study analyzed all patients ( n = 1920) who underwent curative postoperative breast cancer radiotherapy at our institution between May 2020 and December 2024. All patients underwent initial DIBH feasibility assessment and were evaluated for completion of radiotherapy with DIBH or conversion to FB technique. A detailed subanalysis was performed for all patients treated in 2023 ( n = 470). Patient-related factors including age, body mass index (BMI), Karnofsky Performance Status (KPS), Charlson Comorbidity Index (CCI), pulmonary comorbidities, smoking status, and geometric surface distance between DIBH and FB planning scans were collected for the subanalysis. Results: Across the entire cohort (years 2020–2024) of 1,920 patients, 78 replannings (4%) occurred due to conversion from DIBH to free breathing. Increasing age (cut-off of 63 years) was significantly associated with higher replanning rates ( p = 0.001). In the 2023 subanalysis ( n = 470), pulmonary comorbidities ( p = 0.008), higher CCI ( p = 0.044), and a geometric surface distance of below 1 cm between DIBH and FB CT scans ( p = 0.0001) were significant predictors of replanning. The Karnofsky Performance Score, BMI, and smoking status showed no significant association with replanning. Conclusions: Age, pulmonary comorbidities, overall comorbidity burden, and insufficient geometric displacement are significant predictors of DIBH failure in breast cancer radiotherapy. These readily available clinical parameters can optimize patient selection algorithms and inform decisions regarding dual CT simulation workflows. A risk-stratified approach incorporating these factors may reduce unnecessary imaging, decrease planning burden, and improve resource allocation while maintaining optimal cardiac protection for appropriate candidates. Clinical trial number: The study was registered in the German Clinical Trials Register (DRKS; registration number: DRKS00038550) on 22 December 2025 ( https://www.drks.de/ ).

Background/Objectives: The implementation of tattoo-free radiotherapy (RT) for breast cancer reflects an effort to mitigate the psychological distress of permanent marks through surface-guided techniques, while simultaneously evaluating its utility in meeting setup precision requirements. Methods: In this prospective trial, patients were positioned for breast cancer RT including regional nodal irradiation exclusively using surface-guided RT (SGRT). Cone-beam computed tomography (CBCT) was acquired at each fraction as the ground truth to analyze translational setup deviations. Results: A total of 457 paired SGRT–CBCT data points in 30 patients were acquired. A residual translational setup deviation of ≤6 mm was achieved in 97.6% of all fractions with a median deviation of 2 mm (range: 0–12). Neither age, comorbidities, body mass index, extent of target volumes, choice of breathing technique, nor patient-reported symptoms (pain, dermatitis, anxiety) correlated significantly with setup deviations. The median in-room positioning time was 92 s (range: 20 s–6 min and 37 s) and significantly prolonged in patients with an elevated BMI and higher grades of pain and skin dermatitis, and for chest wall irradiation. Manual assessment of the accuracy of regional nodal CTVs in each CBCT relative to the planning CT showed good-to-minor deviations in 99.7% (Level 1/2), 95.0% (Supra-/infraclavicular), and 90.8% (Internal mammary), respectively, with major deviations in only 0.3% (Level 1/2), 5.0% (Supra-/infraclavicular) and 9.2% (Internal mammary). A forward dose calculation on CBCT geometries (n = 86) revealed high median CTV dose coverage of 100.0% (range: 57.1–107.7%) of the original target dose for all lymph node levels combined. Conclusions: The tattoo-free positioning setup for regional nodal irradiation in breast cancer patients exhibited pronounced robustness, maintaining its accuracy and reliability irrespective of patient-, tumor-, or treatment-specific variables with high clinical efficiency. However, larger cohorts are required to confirm whether these parameters genuinely operate independently of setup accuracy.

Background: The irradiation of both breasts poses complex technical challenges. The overlapping treatment fields and large target volumes make dosimetry challenging, while data for hypofractionated regimens in this setting are limited. Methods: Bilateral breast cancer patients treated with moderately hypofractionated and conventionally fractionated radiotherapy were identified to evaluate dosimetric parameters, toxicity, and oncologic outcomes. Results: Seventy patients treated with a median dose of 50.4 Gy in 28 fractions or 40.05 Gy in 15 fractions using 3D-CRT, IMRT, VMAT, or tomotherapy were identified. With a median follow-up of 45.3 months, the 1‑ and 5‑year overall survival rates were 96.1% and 88.7%, and the local control rates were 100% and 92.5%, respectively. The median lung and heart doses were 8.4 and 4.0 Gy for conventional fractionation and 7.6 and 3.1 Gy for hypofractionation, respectively. With conventional fractionation, acute toxicity (≥ grade 3) occurred in 11% of patients (skin), and late toxicity occurred in 4% (skin and cardiac). With hypofractionation, acute toxicity (≥ grade 3) occurred in 8% (skin); no late grade ≥ 3 toxicity was observed. Even though late skin toxicity was more frequent with conventional fractionation, this did not reach statistical significance ( p = 0.056). Regarding RT techniques, only the use of helical tomotherapy was associated with higher incidences of acute ≥ grade 3 skin toxicity ( p = 0.029). Conclusion: Our long-term findings support the use of moderately hypofractionated RT with VMAT as a safe option for bilateral whole-breast irradiation for synchronous bilateral breast cancer, demonstrating favorable outcomes. However, prospective data are still needed, especially for nodal and bilateral chest wall irradiation involving implants.

Introduction: Postoperative active raster-scanning intensity modulated proton beam therapy (IMPT) for gynecological cancers requires precise target coverage, yet interfractional motion of the vaginal cuff and adjacent pelvic organs may compromise dosimetric robustness. This study retrospectively assessed interfractional organ movement and evaluated the clinical need for rectal balloon (RB) use to ensure adequate target coverage. Methods: 23 patients, 17/6 with/without RB, received postoperative IMPT between 2017 and 2020 at Heidelberg Ion-beam Therapy Center (HIT). Positioning verification computed tomography (pv-CT) and treatment planning CT (tp-CT) images were retrieved and rectum, bladder and the vaginal cuff (VC) were contoured. The clinical target volume (CTV) and planning target volume (PTV) were mapped from tp-CT to the pv-CT images and forward dose calculation was performed. To assess the volume of the VC not covered by the CTV or PTV, the region of interest (ROI), VC outside of CTV (VC-CTV) and outside of PTV (VC-PTV) were created. Volume differences (Δ) to the tp-CT images and dose parameters for each ROI were evaluated. Results: 139 pv-CTs were analysed. The use of RB significantly reduced VC displacements, resulting in fewer pv-CTs with the VC located outside the CTV (40% vs. 91%, p = 0.0252) and PTV (28% vs. 68%, p = 0.0362). CTV/PTV coverage and ROI doses remained stable across all fractions and there was no significant difference between groups. The applied PTV margins ensured robust dose coverage despite interfractional anatomical variations. Conclusion: RB application effectively reduced interfractional VC motion and there was no significant Δ in target coverage or ROI doses. Using tp-CT images with full and empty bladder for definition of the CTV and standardized PTV margins contributed to stable dosimetry outcomes, confirming the robustness of the used IMPT treatment protocol. However, the use of RB may be beneficial, especially in patients with known gastrointestinal comorbidities or trapped air in the rectum.

Background: Postoperative recurrence of sacrococcygeal chordomas presents significant clinical challenges due to unusual recurrence patterns. This study aimed to characterize these patterns of recurrence to inform improved adjuvant radiotherapy planning. Methods: We retrospectively analyzed 31 patients with recurrent sacrococcygeal chordoma following surgery, assessing recurrence locations considering initial tumor extent, resection levels, and postoperative anatomical changes on MRI. In 18 patients, pre- and postoperative imaging enabled the spatial mapping of early recurrence origins relative to the initial tumor volume using isotropic expansions. The median initial gross tumor volume was 113 mL. Results: Recurrences were mostly multifocal and predominantly involved soft tissues (e.g., mesorectal/perirectal space (80.6%), piriformis and gluteal muscles (80.6% and 67.7%, respectively) and osseous structures, particularly the sacrum (87.1%)). The median time to recurrence was 15 months. The initial surgery was R0 in 17 patients (55%). The highest infiltrated sacral vertebra was S1 in 3%, S2 in 10%, S3 in 35%, S4 in 23%, S5 in 10%, and coccygeal in 19%. Anatomical changes post-resection, including rectal herniation into gluteal and subcutaneous tissues, significantly affected radiotherapy planning. Expansion of the initial tumor volume by 2 cm failed to encompass all recurrence origins in 72% of cases. A 5 cm expansion was required to achieve full coverage in 56% of patients, though 22% of recurrences still lay beyond this margin and the remaining were covered only partially. Conclusions: Recurrent sacrococcygeal chordomas exhibit complex, soft-tissue-dominant patterns and are influenced by significant anatomical displacement post-surgery. Standard target volume expansions are often insufficient to cover the predominantly multifocal recurrences.

(1) Background: The management of ipsilateral breast cancer recurrence depends on the extent of the tumor, and staging results, and mastectomy is currently the standard of care for previously irradiated patients. Studies are increasingly investigating suitable candidates for the repeated use of breast-conserving approaches as an alternative to mastectomy. But this includes the crucial necessity for curative reirradiation (Re-RT). The therapeutic challenge in reirradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy, intraoperative radiotherapy, or external beam RT with photons or electrons. The application of particle therapy using proton beam therapy represents an innovative radiotherapeutic technique for breast cancer patients that might offer advantageous physical properties, a superior dose reduction to adjacent organs-at-risk, and effective target volume coverage with lower integral doses to the patient’s whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses. (2) Methods: The BREAST trial (NCT06954623) will be conducted as a prospective, single-arm, phase II study in 20 patients with histologically proven invasive breast cancer recurrences after repeat breast-conserving surgery and with an indication for local reirradiation. The patients will receive partial-breast re-RT with proton beam therapy in 15 once-daily fractions up to a total dose of 40.05 Gy(RBE), delivered with active raster scanning. The required time interval will be 1 year after previous RT to the ipsilateral breast. (3) Results: The following results will be reported: The primary endpoint is defined as the cumulative overall occurrence of (sub)acute skin toxicity of grade ≥ 3 within 6 months after the start of re-RT. Secondary outcome includes an analysis of the local, regional, and distant control, progression-free and overall survival, quality of life, and cosmesis. The explorative and translational objectives of this study include planning comparisons to other RT techniques and irradiation types, dosimetric evaluations, analyses of radiological imaging features, and translational assessments of cardiac toxicity biomarkers and tumor markers. (4) Conclusions: Overall, the aim of this study is to evaluate the potential of proton beam therapy for partial breast reirradiation and to establish the underlying data for a randomized trial.

Background/Objectives: Stereotactic body radiotherapy is frequently used in patients with adrenal metastases. Motion of adherent radiosensitive organs at risk (OARs) and tumors influence OAR toxicity and tumor control. Online-adaptive Magnetic Resonance-guided radiotherapy (MRgRT) can address and mitigate interfractional changes. However, the impact of intrafractional variations in adrenal MRgRT is unknown. Methods: A total of 23 patients with 24 adrenal metastases were treated with MRgRT. After daily plan adaptation and before beam application, an additional (preRT) 3d MRI was acquired. PreRT target volumes and OARs were retrospectively recontoured in 200 fractions. The delivered, online-adapted treatment plans, as well as non-adapted baseline plans, were calculated on these re-contoured structures to quantify the dosimetric impact of intrafractional variations on target volume coverage and OAR doses with and without online adaptation. Normal tissue complication probabilities (NTCPs) were calculated. Results: The median time between the two MRIs was 56.4 min. GTV and PTV coverage (dose to 95% of the PTV, D95%, and volume covered by 100% of the prescription dose, V100%) were significantly inferior in the preRT plans. GTV D_mean was significantly impaired in left-sided metastases, but not in right-sided metastases. Compared to non-adapted preRT plans, adapted preRT plans were still significantly superior for all GTV and PTV metrics. Intrafractional violations of OAR constraints were frequent. D0.5cc and the volume exposed to the near-maximum dose constraint were significantly higher in the preRT plans. The volume exposed to the D0.5cc constraints in single fractions escalated up to 1.5 cc for the esophagus, 3.2 cc for the stomach, 5.3 cc for the duodenum and 7.3 cc for the bowel. This led to significantly elevated NTCPs for the stomach, bowel and duodenum. Neither PTV D95%, nor gastrointestinal OAR maximum doses were significantly impaired by longer fraction duration. Conclusions: Intrafractional motion in adrenal MRgRT caused significant impairment of target volume coverage (D95% and V100%), potentially undermining local control. Frequent violation of gastrointestinal OAR constraints led to elevated NTCP. Compared to non-adaptive treatment, online adaptation still highly improved GTV and PTV coverage.

This study investigates the clinical efficacy of MRI-based adaptive brachytherapy (IGABT) using combined intracavitary and interstitial techniques in the curative treatment of patients with advanced cervical cancer (LACC). A retrospective analysis was conducted on 149 LACC patients treated at a single center. The therapeutic protocol included intensity-modulated external beam radiotherapy (IMRT) and IGABT. Dosimetric parameters were evaluated for relevance for local control (LC), progression-free survival (PFS), and overall survival (OS) using Kaplan–Meier estimation, Cox regression, and log-rank test. Patients predominantly presented with stage III/IV tumors (81%, FIGO 2018). The median high-risk clinical target volume (hrCTV) was 34 cm³, with a median D90% dose of 88.9 GyEQD2. At 24 months, OS, PFS, and LC rates were 86%, 57%, and 81%, respectively. FIGO stage, tumor volume, and histology were significant predictors of PFS. Higher total hrCTV doses were strongly correlated with improved LC and PFS, emphasizing the importance of precise dosimetric optimization in IGABT and confirming the critical role of IGABT in achieving very good LC rates for LACC. The reported LC rates are comparable to landmark studies, such as INTERLACE and KEYNOTE-A18. This study validates the effectiveness of MRI-guided IGABT in enhancing local tumor control in advanced-stage cervical cancer while providing insights into the prognostic implications of dosimetric parameters such as hrCTV and point A. Future research should address the persistent challenge of distant metastases by exploring the integration of novel systemic treatment options.