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However, the fixed beam optimization method has not considered the effects of beam orientation on the dose and dose rates. To maximize the proton FLASH effect, here, we incorporate dose rate objectives into our beam orientation optimization framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From our previously developed group\u2010sparsity dose objectives, we add upper and lower dose rate terms using a surrogate dose\u2010averaged dose rate definition and solve using the fast\u2010iterative shrinking threshold algorithm. We compare the dosimetry for three head\u2010and\u2010neck cases between four techniques: (1) spread\u2010out BP IMPT (BP), (2) dose rate optimization using BP beams only (BP\u2010DR), (3) dose rate optimization using ST beams only (ST\u2010DR), and (4) dose rate optimization using combined BP and ST (BPST\u2010DR), with the goal of sparing organs at risk without loss of tumor coverage and maintaining high dose rate within a 10\u00a0mm region of interest (ROI) surrounding the clinical target volume (CTV).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For BP, BP\u2010DR, ST\u2010DR, and BPST\u2010DR, CTV homogeneity index and Dmax were found to be on average 0.886, 0.867, 0.687, and 0.936 and 107%, 109%, 135%, and 101% of prescription, respectively. Although ST\u2010DR plans were not able to meet dosimetric standards, BPST\u2010DR was able to match or improve either maximum or mean dose in the right submandibular gland, left and right parotids, constrictors, larynx, and spinal cord compared to BP plans. Volume of ROIs receiving greater than 40\u00a0Gy\/s ( was 51.0%, 91.4%, 95.5%, and 92.1% on average.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The dose rate techniques, particularly BPST\u2010DR, were able to significantly increase dose rate without compromising physical dose compared with BP. Our algorithm efficiently selects beams that are optimal for both dose and dose rate.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.16009","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T09:44:17Z","timestamp":1665567857000},"page":"7826-7837","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dose and dose rate objectives in Bragg peak and shoot\u2010through beam orientation optimization for FLASH proton therapy"],"prefix":"10.1002","volume":"49","author":[{"given":"Pavitra","family":"Ramesh","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_180_20"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864\u2010018\u20100546\u20109"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.12954"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13193\u2010010\u20100030\u2010x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meddos.2021.02.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2018.11.015"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2019.04.001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186492"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2020.1704912"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13164244"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13051012"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.05.005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/abcbd0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.14933"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.15659"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.15579"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/abaa28"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2015.02.001"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.02.009"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.14531"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201020\u20100894"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.09.011"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2022.100954"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.15276"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.813063"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.11.011"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2022.01.009"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106560\/ac02d8"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13225790"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.15356"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2019.1627416"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.14456"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.13641"},{"key":"e_1_2_8_35_1","doi-asserted-by":"crossref","unstructured":"BeckA TeboulleM.A fast iterative shrinkage\u2010thresholding algorithm with application to wavelet\u2010based image deblurring. 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