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.
Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.
Stereotactic body image guided radiation therapy (SBRT) shows excellent results for the local control of early stage lung cancer. However, not all patients are eligible for SBRT, and advanced stage treatment is less successful and often associated with severe side effects. Scanned carbon ion therapy (PT) can deliver more conformal dose likely benefiting these patient groups.Therefore an in silico trial was conducted on early and advanced stage patients to identify potential advantages of PT. The patients were treated with SBRT at Champalimaud Center for the Unknown, Lisbon (Portugal). PT plans were simulated on 4DCTs, and rescanning was investigated for motion mitigation in 4D-dose calculations. A dedicated strategy for 4D intensity modulated particle therapy (IMPT) was developed and applied for advanced stage patients with multiple lesions. For clinically valid and reliable results the deformable image registrationnecessary for 4D-dose calculation -a quality assurance tool was developed and applied in the study.The results showed that target coverage was comparable in SBRT and PT, while PT delivered significantly lower doses to most critical structures, especially the heart, lungs, and esophagus.A highly complex case of advanced stage lung cancer could be treated in a single fraction of 24 Gy with PT, while SBRT could not deliver the full ablative dose treatment due to an excessive heart dose. The mean heart dose was reduced from 10 Gy to 0.8 Gy with PT for this specific patient.
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