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Christian Graeff

Publications and source records attributed to Christian Graeff.

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Mixed Ion Beams Enable Simultaneous Treatment and Real-Time Imaging in Carbon Ion Therapy

Carbon ion therapy is one of the most advanced forms of radiotherapy, promising improved efficacy against resistant cancers. However, the high precision offered by the carbon ion Bragg peak requires precise knowledge of the beam range inside the patient. We report the first experimental realization of range monitoring and portal imaging with a mixed ion beam, where carbon ions are treating the tumor while helium ions simultaneously accelerated to the same velocity fully traverse the patient and provide treatment feedback. Using the GSI synchrotron, a beam of 12C3+ and 4He1+ ions is accelerated, exploiting their nearly identical charge-to-mass ratios. Stable extraction with controlled helium fractions down to 7% is demonstrated. Beam characterization reveals that the helium ion Bragg peak can be cleanly separated from the carbon ion fragment background which enables accurate detection of sub-millimeter Bragg peak displacements. Mixed-beam radiographs of a lung-cancer-like phantom offer target position detection to better than 0.5 mm accuracy. This establishes mixed beams as a powerful modality for real-time image guidance in carbon ion therapy, uniquely providing simultaneous treatment delivery, range probing, and portal imaging. By overcoming range uncertainty inside the patient, mixed beams will enable to fully exploit the precision of carbon ion therapy.

physics.med-ph

Dosimetric Study of Lung Modulation and Motion Effects in Carbon ion Therapy for Lung Cancer

Carbon-ion radiotherapy provides high dose conformity for lung cancer, but its benefit is limited by two sources of uncertainties: interplay between scanned beam delivery and tumor motion, and dose modulation from heterogeneous lung tissue. This study quantifies the separate and combined dosimetric impact of these effects using the GSI TRiP4D treatment planning system. Eighteen lung cancer 4DCT datasets from TCIA were analyzed. A modulation power ($P_{\mathrm{mod}}$) was assigned to lung voxels. Three values were sampled from a Gaussian distribution ($200\mu\mathrm{m} \pm 67\mu\mathrm{m}$), and an extreme value of $750\mu\mathrm{m}$ was tested. Interplay doses were computed by combining scanned-beam delivery with patient-specific respiratory motion. Four scenarios were studied: static, static with modulation, interplay, and interplay with modulation. Metrics included $D95\%$, $V95\%$, homogeneity index (HI), lung $V16\mathrm{Gy}$, and heart $V20\mathrm{Gy}$. Interplay reduced target coverage by $5.2 \pm 1.5$ pp ($D95\%$), $12.1 \pm 5.9$ pp ($V95\%$), and $8.3 \pm 2.4$ pp (HI). Extreme $P_{\mathrm{mod}}$ alone caused small degradations. When combined with interplay, it partially compensated the loss. This effect decreased with 4D optimization. Fractionation mitigated interplay, leaving lung modulation as the main residual effect.

physics.med-ph

An AI dose engine for fast carbon ion treatment planning

Monte Carlo (MC) simulations provide gold-standard accuracy for carbon ion therapy dose calculations but are computationally intensive. Analytical pencil beam algorithms offer speed but reduced accuracy in heterogeneous tissues. We developed the first AI-based dose engine capable of predicting absorbed dose, the alpha and beta parameters for relative biological effectiveness (RBE)- weighted optimisation in carbon ion therapy, delivering MC-level accuracy with drastically reduced computation time. We extended the transformer-based DoTA model to predict absorbed dose (C-DoTA-d), alpha (C-DoTA-alpha), and beta (C-DoTA-beta), introducing a cross-attention mechanism for alpha and beta to combine dose and energy inputs. The training dataset consisted of ~70,000 pencil beams from 187 head-and-neck patients, with ground-truth values obtained using the GPU-accelerated MC toolkit FRED. Performance was evaluated on an independent test set using gamma pass rate (1%/1 mm), depth-dose, and isodose contour Dice coefficients. MC dropout-based uncertainty analysis was performed. Median gamma pass rates exceeded 98% for all predictions (99.76% for dose, 99.14% for alpha, and 98.74% for beta), with minima above 85% in the most heterogeneous anatomies. The Dice coefficient was 0.95 for 1% isodose contours, with slightly reduced agreement in high-gradient regions. Compared to MC FRED, inference was over 400x faster (0.032 s vs. 14 s per pencil beam) while maintaining accuracy. Uncertainty analysis showed high stability, with mean standard deviations below 0.5% for all models. C-DoTA achieves MC-quality predictions of absorbed dose and RBE model parameters in ~30 milliseconds per beam. Its speed and accuracy support online adaptive planning, paving the way for more effective carbon ion therapy workflows. Future work will expand to additional anatomical sites, beam geometries, and clinical beamlines.

physics.med-ph

First image-guided treatment of a mouse tumor with radioactive ion beams

Radioactive ion beams (RIB) are a key focus of current research in nuclear physics. Already long ago it was proposed that they could have applications in cancer therapy. In fact, while charged particle therapy is potentially the most effective radiotherapy technique available, it is highly susceptible to uncertainties in the beam range. RIB are well-suited for image-guided particle therapy, as isotopes that undergo \b{eta}+-decay can be precisely visualized using positron emission tomography (PET), enabling accurate real-time monitoring of the beam range. We successfully treated a mouse osteosarcoma using a radioactive 11C-ion beam. The tumor was located in the neck, in close proximity to the spinal cord, increasing the risk of radiation-induced myelopathy from even slight variations in the beam range caused by anatomical changes or incorrect calibration of the planning CT. We managed to completely control the tumor with the highest dose while minimizing toxicity. Low-grade neurological side effects were correlated to the positron activity measured in the spine. The biological washout of the activity from the tumor volume was dependent on the dose, indicating a potential component of vascular damage at high doses. This experiment marks the first instance of tumor treatment using RIB and paves the way for future clinical applications.

physics.med-ph

Range margin reduction in carbon ion therapy: potential benefits of using radioactive ion beams

Radiotherapy with heavy ions, in particular, 12C beams, is one of the most advanced forms of cancer treatment. Sharp dose gradients and high biological effectiveness in the target region make them an ideal tool to treat deep-seated and radioresistant tumors, however, at the same time, sensitive to small errors in the range prediction. Safety margins are added to the tumor volume to mitigate these uncertainties and ensure its uniform coverage, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the benefits of a sharp Bragg peak, a large effort is put into establishing precise range verification methods for the so-called image-guided radiotherapy. Despite positron emission tomography being widely in use for this purpose in 12C ion therapy, the low count rates, biological washout, and broad shape of the activity distribution still limit its precision to a few millimeters. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C beams treatments, on sparing critical organs in the tumor proximity. We demonstrate that (i) annihilation maps for 11C ions can in principle reflect even millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C beams are significantly improved in terms of meeting the constraints for the organs at risk compared to 12C plans, and (iii) less severe toxicities for serial and parallel critical organs can be expected following 11C treatment with reduced range uncertainties, compared to 12C treatments.

physics.med-ph