To improve outcomes in large sarcomas/chordomas treated with CIRT, there has been recent interest in LET optimization. We evaluated 22 pelvic sarcoma/chordoma patients treated with CIRT [large: HD-CTV ≥ 250 cm³ (n = 9), small: HD-CTV < 250 cm³ (n = 13)], D_RBE|LEM-I = 73.6 (70.4–73.6) Gy (RBE)/16 fractions, using the local effect model-I (LEM-I) optimization and modified-microdosimetric kinetic model (mMKM) recomputation. We observed that to improve high-LETd distribution in large tumors, at least 27 cm³ (low-LETd region) of HD-CTV should receive LETd of ≥33 keV/µm (p < 0.05). Hence, LETd optimization using ‘distal patching’ was explored in a treatment planning setting (not implemented clinically yet). Distal-patching structures were created to stop beams 1–2 cm beyond the HD-PTV-midplane. These plans were reoptimized and D_RBE|LEM-I, D_RBE|mMKM, and LETd were recomputed. Distal patching increased (a) LETd50% in HD-CTV (from 38 ± 3.4 keV/µm to 47 ± 8.1 keV/µm), (b) LETdmin in low-LETd regions of the HD-CTV (from 32 ± 2.3 keV/µm to 36.2 ± 3.6 keV/µm), (c) the GTV fraction receiving LETd of ≥50 keV/µm, (from 50%) and (d) the high-LETd component in the central region of the GTV, without significant compromise in D_RBE distribution. However, distal patching is sensitive to setup/range uncertainties, and efforts to ascertain robustness are underway, before routine clinical implementation.

To minimize radiation-induced lumbosacral neuropathy (RILSN), we employed sacral-nerve-sparing optimized carbon-ion therapy strategy (SNSo-CIRT) in treating 35 patients with pelvic sarcomas/chordomas. Plans were optimized using Local Effect Model-I (LEM-I), prescribed D_{RBE|LEM-I|D50%} (median dose to HD-PTV) = 73.6 (70.4–76.8) Gy (RBE)/16 fractions. Sacral nerves were contoured between L5-S3 levels. D_RBE|LEM-I to 5% of sacral nerves-to-spare (outside HD-CTV) (D_{RBE|LEM-I|D5%}) were restricted to <69 Gy (RBE). The median follow-up was 25 months (range of 2–53). Three patients (9%) developed late RILSN (≥G3) after an average period of 8 months post-CIRT. The RILSN-free survival at 2 years was 91% (CI, 81–100). With SNSo-CIRT, D_{RBE|LEM-I|D5%} for sacral nerves-to-spare = 66.9 ± 1.9 Gy (RBE), maintaining D_RBE|LEM-I to 98% of HD-CTV (D_{RBE|LEM-I|D98%}) = 70 ± 3.6 Gy (RBE). Two-year OS and LC were 100% and 93% (CI, 84–100), respectively. LETd and D_RBE with modified-microdosimetric kinetic model (mMKM) were recomputed retrospectively. D_RBE|LEM-I and D_RBE|mMKM were similar, but D_RBE-filtered-LETd was higher in sacral nerves-to-spare in patients with RILSN than those without. At D_RBE|LEM-I cutoff = 64 Gy (RBE), 2-year RILSN-free survival was 100% in patients with 55 keV/µm than 75% (CI, 54–100) in those with ≥12% of voxels (p < 0.05). D_RBE-filtered-LETd holds promise for the SNSo-CIRT strategy but requires longer follow-up for validation.

Background and purpose: Autocontouring for radiotherapy has the potential to significantly save time and reduce interobserver variability. We aimed to assess the performance of a commercial autocontouring model for head and neck (H&N) patients in eight orientations relevant to particle therapy with fixed beam lines, focusing on validation and implementation for routine clinical use. Materials and methods: Autocontouring was performed on sixteen organs at risk (OARs) for 98 adult and pediatric patients with 137 H&N CT scans in eight orientations. A geometric comparison of the autocontours and manual segmentations was performed using the Hausdorff Distance 95th percentile, Dice Similarity Coefficient (DSC) and surface DSC and compared to interobserver variability where available. Additional qualitative scoring and dose-volume-histogram (DVH) parameters analyses were performed for twenty patients in two positions, con-sisting of scoring on a 0-3 scale based on clinical usability and comparing the mean (Dmean) and near-maximum (D2%) dose, respectively. Results: For the geometric analysis, the model performance in head-first-supine straight and hyperextended orientations was in the same range as the interobserver variability. HD95, DSC and surface DSC was heteroge-neous in other orientations. No significant geometric differences were found between pediatric and adult autocontours. The qualitative scoring yielded a median score of >= 2 for 13/16 OARs while 7/32 DVH parameters were significantly different. Conclusions: For head-first-supine straight and hyperextended scans, we found that 13/16 OAR autocontours were suited for use in daily clinical practice and subsequently implemented. Further development is needed for other patient orientations before implementation.

Purpose: Head and neck mucosal melanomas (HNMMs) are aggressive, radiotherapy-resistant cancers. Previous JCROS studies demonstrated improved local control with carbon-ion radiotherapy (CIRT). This study evaluates early outcomes of CIRT for HNMM using the European and Japanese relative biological effectiveness (RBE)adapted dose prescriptions. Materials and Methods: Between November 2019 and April 2023, 14 HNMM patients received CIRT treatment. Postoperative CIRT for R2 resection: 9 cases; biopsies only: 5 cases. Immune checkpoint inhibitors used as primary treatment: 6 cases; salvage: 8 cases. CIRT delivered in D-RBE dose of 68.8 (64.5-68.8) Gy (RBE)/16 fractions, optimized with the local effect model I (LEM-I, European) for RBE-weighted dose, recalculated using the modified-microdosimetric kinetic model (mMKM, Japanese). Results: HHNMM tumor and nodal stages: cT3: 2 (14%), cT4: 12 (86%), cN1: 1 (7%). The median follow-up was 22 months (range, 4-54). The 2-year local recurrence-free survival, regional recurrence-free survival, overall survival, and distant metastasis-free survival were 100%, 89% (CI, 71-100), 64% (CI, 44-95), and 43% (CI, 22-84), respectively. The median relative volumetric tumor regression at 3, 6, and 12 months post-CIRT was 40%, 63%, and 72%, respectively. CIRT-associated late toxicities were G3 mucositis: 2 (14%) and G3 anosmia: 1 (7%). The immune checkpoint inhibition-related late toxicities were G2 hypophysitis: 1 (11%) and G3 peripheral neuropathy: 1 (11%). The average attainable D-RBE coverage for 95% of high-dose clinical target volume was 63.2 +/- 6 Gy (RBE) (LEM-I) and 57.4 +/- 5 Gy (RBE) (mMKM). The LETd distribution in high-dose clinical target volume was satisfactory, LETd(50%) (median) = 57.3 +/- 6 keV/mu m and LETd(98%) (near minimum) = 46.5 +/- 6.1 keV/mu m. Conclusion: Bi-RBE model (LEM-I, mMKM) optimized CIRT protocol improved dose comparability of plans between different systems. It also improved intratumoral LETd distribution and resulted in rapid tumor regression, favorable toxicity profile, and excellent early loco-regional control. It provides a promising alternative to surgery, though distant metastasis remains the key prognostic factor.

In head and neck carbon-ion radiotherapy (CIRT), high dose-averaged LET (LETd) and relative biological effectiveness weighted dose (D_RBE) often overlap the oro-pharyngeal-mucosa (mucosa of oral cavity, oro-pharynx, nasopharynx, pharynx) beyond the target, resulting in serious complications. We investigated clinical and dosimetric predictors for late severe mucosal-toxicity/ oro-antral fistula (OAF) post-CIRT. CIRT plans for 51 patients with non-squamous head and neck cancers (NSHNCs) were evaluated and correlated with clinical outcome. Prescription was D_RBE of 68.8 Gy (65.6-76.8)/16 fractions optimized using Local Effect Model-I (LEM-I). After the first 21 patients a mucosa-sparing approach (MS-CIRT) was adopted, delineating healthy mucosa-to-spare within the high-dose PTV and applying D_RBE constraints (D_RBE|0.1cm3 < 70 Gy), maintaining target coverage. For the present analysis, D_RBE was recomputed also with the modified microdosimetric kinetic model (mMKM) and LETd was calculated. Several clinical and dosimetric parameters including DLV-parameters (61 Gy ≤ D_RBE ≤ 70 Gy, LETd ≥ 50 keV/µm, volume) that may be predictors of OAF were analyzed. MS-CIRT reduced mucosal doses to < 70 Gy, preserving local control (preliminary results in limited number of patients). Seven patients developed late G3 OAF after median follow-up of 23 months, including 2 with MS-CIRT. Doses to oro-pharyngeal mucosa > 70 Gy were predictive of OAF development. Even moderate-high doses correlated with OAF if they coincided with high-LETd. For instance, when more than 1 cm³ of mucosa-to-spare was exposed to D_RBE|mMKM ≥ 63 Gy and LETd ≥ 75 keV/µm, 2-yr OAF-free survival probability was 38 % versus 100 % in cases where these thresholds were not exceeded (p < 0.001). Sino-nasal primary and HD-CTV ≥ 100 cm³ also influenced OAF development. Besides MS-CIRT strategy, optimizing DLV-parameters for oro-pharyngeal-mucosa may be a promising strategy in preventing late G3 OAF post-CIRT.

Background and Purpose: Helium ions combine reduced lateral scattering compared to protons and a lower fragmentation tail than carbon ions, enabling sharp dose gradients and improved normal tissue sparing. This study reports the commissioning of a scanned helium pencil beam line and implementation of its corresponding beam model, complementing existing proton and carbon ion commissioning data. Materials and Methods: Synchrotron-based helium beams were commissioned covering energies from 54.6 to 402.8 MeV/u. Depth–dose curves were measured and absolute dose calibration performed. Beam optics (spot size, position, and intraspill stability) were evaluated for various spill lengths. A beam model was implemented in the treatment planning system (TPS) RayStation v2024A and validated through 2D absolute dose measurements and 3D measurements of cubic spread-out Bragg peak fields. Gamma-index analysis (3 %/1.5 mm and 5 %/1.5 mm) and Monte Carlo (MC) simulations with GATE/Geant4 were performed for benchmarking. Results: Measured ranges agreed with MC simulations within ±0.3 mm. Spot sizes decreased with energy, independently of spill length. Spot positions remained within ±0.5 mm and intraspill variations were ≤0.2 mm (position) and ≤5.4 % (size). TPS-predicted doses agreed within 0.1 %. For 3D validations, dose differences were generally within 2 %, with larger deviations limited to high-gradient regions and range shifter configurations. Gamma pass rates exceeded 95 % for 5 %/1.5 mm and 90 % for 3 %/1.5 mm. Conclusions: The helium pencil beam line was successfully commissioned and validated, demonstrating strong agreement between measurements, TPS calculations, and MC simulations, supporting future research and clinical application.