% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Liu:265116, author = {R. Liu and S. Charyyev and N. Wahl$^*$ and W. Liu and M. Kang and J. Zhou and X. Yang and F. Baltazar$^*$ and M. Palkowitsch$^*$ and K. Higgins and W. Dynan and J. Bradley and L. Lin}, title = {{A}n {I}ntegrated {P}hysical {O}ptimization framework for proton {SBRT} {FLASH} treatment planning allows dose, dose rate, and {LET} optimization using patient-specific ridge filters.}, journal = {International journal of radiation oncology, biology, physics}, volume = {116}, number = {4}, issn = {0360-3016}, address = {Amsterdam [u.a.]}, publisher = {Elsevier Science}, reportid = {DKFZ-2023-00278}, pages = {949-959}, year = {2023}, note = {2023 Jul 15;116(4):949-959}, abstract = {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 ultra-high dose rate (FLASH) radiotherapy. We demonstrate an Integrated Physical Optimization IMPT (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged LET (LETd).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 (BSPTV). 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 MU 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 three example lung cancer patients and optimized the plans using IPO-IMPT.The IPO-IMPT framework selectively spared the OARs 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 BSPT.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.}, keywords = {FLASH (Other) / IMPT (Other) / LET (Other) / Patient-specific ridge filter (Other) / SBPT (Other) / dose rate (Other) / integrated physical optimization (Other) / sparse optimized ridge filter (Other)}, cin = {E040}, ddc = {610}, cid = {I:(DE-He78)E040-20160331}, pnm = {315 - Bildgebung und Radioonkologie (POF4-315)}, pid = {G:(DE-HGF)POF4-315}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:36736634}, doi = {10.1016/j.ijrobp.2023.01.048}, url = {https://inrepo02.dkfz.de/record/265116}, }