RESUMO
PURPOSE: To analyze the dose objectives and constraints applied at the prospective phase II PACK-study at Heidelberg ion therapy center (HIT) for different radiobiological models. METHODS: Treatment plans of 14 patients from the PACK-study were analyzed and recomputed in terms of physical, biological dose and dose-averaged linear energy transfer (LETd). Both LEM-I (local effect model 1) and the adapted NIRS-MKM (microdosimetric kinetic model), were used for relative biological effectiveness (RBE)-weighted dose calculations (DBio|HIT and DBio|NIRS). A new constraint to the gastrointestinal (GI) tract was derived from the National Institute of Radiological Science (NIRS) clinical experience and considered for plan reoptimization (DBio|NIRS-const_48Gy and DBio|NIRS-const_50.4Gy). The Lyman-Kutcher-Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for GI toxicity endpoints was computed. Furthermore, the computed LETd distribution was evaluated and correlated with Local Control (LC). RESULTS: Only two patients showed a LETd98% in the GTV greater than 44 keV/µm. A HIT-dose constraint to the GI of [Formula: see text] was derived from the NIRS experience, in alternative to the standard at HIT Dmax = 45.6 GyRBEHIT. In comparison with the original DBio|HIT,DBio|NIRS-const_48GyandDBio|NIRS-const_50.4Gy resulted in an increase in the ITV's D98% of 8.7% and 11.3%. The NTCP calculation resulted in a probability for gastrointestinal bleeding of 4.5%, 12.3% and 13.0%, for DBio|NIRS, DBio|NIRS-const_48Gy and DBio|NIRS-const_50.4Gy, respectively. CONCLUSION: The results indicate that the current standards applied at HIT for CIRT closely align with the Japanese experience. However, to enhance tumor coverage, a more relaxed constraint on the GI tract may be considered. As the PACK-trial progresses, further analyses of various clinical endpoints are anticipated.
RESUMO
PURPOSE: Patient-specific ridge filters provide a passive means to modulate proton energy to obtain a conformal dose. Here we describe a new framework for optimization of filter design and spot maps to meet the unique demands of ultrahigh-dose-rate (FLASH) radiation therapy. We demonstrate an integrated physical optimization Intensity-modulated proton therapy (IMPT) (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged linear energy transfer (LETd). METHODS AND MATERIALS: We developed an inverse planning software to design patient-specific ridge filters that spread the Bragg peak from a fixed-energy, 250-MeV beam to a proximal beam-specific planning target volume. The software defines patient-specific ridge filter pin shapes and uses a Monte Carlo calculation engine, based on Geant4, to provide dose and LET influence matrices. Plan optimization, using matRAD, accommodates the IPO-IMPT objective function considering dose, dose rate, and LET simultaneously with minimum monitor unit constraints. The framework enables design of both regularly spaced and sparse-optimized ridge filters, from which some pins are omitted to allow faster delivery and selective LET optimization. To demonstrate the framework, we designed ridge filters for 3 example patients with lung cancer and optimized the plans using IPO-IMPT. RESULTS: The IPO-IMPT framework selectively spared the organs at risk by reducing LET and increasing dose rate, relative to IMPT planning. Sparse-optimized ridge filters were superior to regularly spaced ridge filters in dose rate. Depending on which parameter is prioritized, volume distributions and histograms for dose, DADR, and LETd, using evaluation structures specific to heart, lung, and esophagus, show high levels of FLASH dose-rate coverage and/or reduced LETd, while maintaining dose coverage within the beam specific planning target volume. CONCLUSIONS: This proof-of-concept study demonstrates the feasibility of using an IPO-IMPT framework to accomplish proton FLASH stereotactic body proton therapy, accounting for dose, DADR, and LETd simultaneously.
