Background: Pancreatic cancer is one of the most aggressive and lethal cancers. New treatment strategies are highly warranted. Particle radiotherapy could offer a way to overcome the radioresistant nature of pancreatic cancer because of its biological and physical characteristics. Within particles, helium ions represent an attractive therapy option to achieve the highest possible conformity while at the same time protecting the surrounding normal tissue. The aim of this study was to evaluate the cytotoxic efficacy of helium ion irradiation in pancreatic cancer in vitro. Methods: Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and helium ions at various doses and treated with gemcitabine. Photon irradiation was performed with a biological cabin X-ray irradiator, and helium ion irradiation was performed with a spread-out Bragg peak using the raster scanning technique at the Heidelberg Ion Beam Therapy Center (HIT). The cytotoxic effect on pancreatic cancer cells was measured with clonogenic survival. The survival curves were compared to the predicted curves that were calculated via the modified microdosimetric kinetic model (mMKM). Results: The experimental relative biological effectiveness (RBE) of helium ion irradiation ranged from 1.0 to 1.7. The predicted survival curves obtained via mMKM calculations matched the experimental survival curves. Mainly additive cytotoxic effects were observed for the cell lines AsPC-1, BxPC-3 and Panc-1. Conclusion: Our results demonstrate the cytotoxic efficacy of helium ion radiotherapy in pancreatic cancer in vitro as well as the capability of mMKM calculation and its value for biological plan optimization in helium ion therapy for pancreatic cancer. A combined treatment of helium irradiation and chemotherapy with gemcitabine leads to mainly additive cytotoxic effects in pancreatic cancer cell lines. The data generated in this study may serve as the radiobiological basis for future experimental and clinical works using helium ion radiotherapy in pancreatic cancer treatment.

Background/Objectives: Head and neck paragangliomas (HNPGs) are rare, typically benign, hypervascular tumors arising from neural crest cells. Although surgery is known as the primary treatment, radiotherapy (RT) is preferred for large and inoperable tumors. This study evaluated the results and safety of RT. Methods: Fifteen patients with radiologically or histologically confirmed HNPG treated with RT between 2001 and 2024 were retrospectively analyzed. Most patients received intensity-modulated radiotherapy (IMRT) with a median dose of 45 Gy. Treatment-related toxicities were graded according to CTCAE criteria. Local control (LC) was estimated with using Wilson score method. Results: With a median follow-up of 96 months, all patients achieved stable or improved symptomes, without local recurrence, resulting in a 100% LC rate. RT was well tolerated, with no acute or late toxicities ≥ grade 2. Conclusions: RT, particularly IMRT, provides excellent long-term LC with minimal toxicity in patients with HNPG. RT represents an effective and well-tolerated treatment option, especially for patients with unresectable disease or high surgical risk.

Background/Objectives: D-dimer, a fibrin degradation product, is associated with tumor growth and metastasis. In breast cancer, high concentrations of D-dimer are linked to more advanced disease stages and metastatic spread. This research aimed to examine the relevance of D-dimer levels in estrogen and progesterone hormone receptor (HR)-positive breast cancer. Methods: This retrospective single-center cohort study included patients with HR-positive breast carcinoma who underwent adjuvant or palliative radiotherapy in Türkiye. Pre- and post-radiotherapy blood test results, including D-dimer levels, were required. D-dimer, lymphocyte percentage, and interleukin-6 levels were measured for evaluation. All statistical analyses were performed using R software (version 4.4.2) to evaluate associations between D-dimer levels and other laboratory parameters. Univariate and multivariate Cox proportional hazards regression were performed to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). Statistical significance was defined as p < 0.05. Results: Elevated D-dimer levels were associated with worse Eastern Cooperative Oncology Group performance status, advanced disease stages, metastasis, elevated IL-6 and CRP levels, and lower lymphocyte counts. Pre-RT D-dimer was a strong prognostic factor. Patients with D-dimer ≤ 0.3 µg/mL showed significantly superior OS and PFS (>60 months; p < 0.001), with only one event, and this remained significant in multivariate analysis (OS: HR 4.55, 95% CI 1.89–11.3; p = 0.002; PFS: HR 3.43, 95% CI 1.54–7.8; p = 0.004). Similarly, D-dimer ≤ 0.5 µg/mL was associated with improved OS (4/72 vs. 19/40 events; p < 0.001) and longer PFS, confirmed in multivariate analysis (OS: HR 4.37, 95% CI 1.72–9.86; p = 0.002; PFS: HR 3.88, 95% CI 1.67–9.1; p = 0.003), whereas levels > 0.5 µg/mL predicted worse outcomes. Using a 0.65 µg/mL cutoff, patients with D-dimer > 0.65 µg/mL had significantly shorter OS (median 25.5 months; 95% CI, 18–NA) compared with those ≤0.65 µg/mL (median not reached; p < 0.001), and this remained independently significant (OS: HR 5.10, 95% CI 1.9–13.6; p < 0.001; PFS: HR 4.68, 95% CI 1.83–11.9; p = 0.002). Conclusions: D-dimer is an accessible, non-invasive biomarker with predictive and prognostic significance in HR-positive breast cancer. Elevated D-dimer levels are suggestive of a more aggressive disease and poorer survival outcomes. This has the potential to facilitate early assessment of treatment efficacy and disease progression. This study has several limitations. Its retrospective, single-center design may introduce selection bias and limit generalizability. Although the sample size was sufficient to detect significant associations, validation in larger, multi-center cohorts is warranted to confirm the prognostic value of D-dimer.

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.