This article describes the updated GSI radiotherapy research facility (Cave M) located at the GSI Helmholtz Center for Heavy Ion Research in Darmstadt, Germany. This facility was upgraded by modernizing the beamline that supported a pilot project in carbon ion cancer therapy in Europe from 1997 to 2008. Descriptions are provided of the modernized beamline, related hardware components and treatment delivery system. The performance specifications and general characteristics for each major component are described, along with example pre-clinical test results of selected components. These upgrades to Cave M allow for investigating novel therapy methods. The radiotherapy research facility is located on a beamline of the heavy ion synchrotron (Schwer-Ionen-Synchrotron, or SIS-18) accelerator complex, capable of delivering 0.1 to 2 GeV/u charged particle beams, ranging from protons to uranium. This beamline contains components for fast beam gating, aborting, focusing, scanning, monitoring, and shifting the range of the beam. The beam scanning magnets, position detectors, and beam monitors are described, along with tests of functionality and performance. A dose delivery system (DDS) was adapted from a clinical unit at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy, and consists of modular real-time hardware and software. The DDS was modified to enable research on adaptively-managed patient motion through the use of libraries of 4D-optimized radiation treatment plans, an unsolved problem of importance for treating moving tumors. The system is modular and is designed to support future research studies, such as high dose rate (Flash) radiotherapy and radioactive ion beams. A series of validation tests confirmed the functionality and performance of various key components and systems. For example, an end-to-end test revealed that dosimetric spatial homogeneity of over 95% was achieved for square treatment fields. More generally, all performance characteristics that were tested satisfied anticipated clinical requirements.

Intensity modulated particle therapy (IMPT) with carbon ions can generate highly conformal treatment plans; however, IMPT is limited in robustness against range and positioning uncertainty. This is particularly true for moving targets, even though all motion states of a 4DCT are considered in 4D-IMPT. Here, we expand 4D-IMPT to include robust non-linear RBE-weighted optimization to explore its potential in improving plan robustness and sparing critical organs. In this study, robust 4D-optimization-based on worst-case optimization on 9 scenarios-was compared to conventional 4D-optimization with PTV margins using 4D dose calculation and robustness analysis for 21 uncertainty scenarios. Slice-by-slice rescanning was used for motion mitigation. Both 4D-optimization strategies were tested on a cohort of 8 multi-lesion lung cancer patients with the goal of prioritizing OAR sparing in a hypofractionated treatment plan. Planning objectives were to keep the OAR volume doses below corresponding limits while simultaneously achieve CTV coverage with D95% ≥ 95 %. For the conventional plans, average D95% was at 98.7% which fulfilled the target objective in 83.2% of scenarios. For the robust plans, average D95% was reduced to 97.6% which still fulfilled the target objective in 80.7% of cases, but led to significantly improved overall OAR sparing: Volume doses were below the limits in 96.2% of cases for the conventional and 99.5% for the robust plans. When considering the particularly critical smaller airways only, fulfillment rates could be increased from 76.2% to 96% for the robust plans. This study has shown that plan robustness of 4D-IMPT could be improved by using robust 4D-optimization, offering greater control over uncertainties in the actual delivered dose. In some cases, this required sacrificing target coverage for the benefit of better OAR sparing.