{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:10:08Z","timestamp":1792001408170,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non\u2013small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity\u2010modulated radiotherapy (IMRT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with locally advanced non\u2013small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either\u00a0IMRT or PBT \u00b1 consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90\u2010day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan\u2013Meier method was used for progression\u2010free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) and had higher Charlson Comorbidity Index scores (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.02). The PBT group received a lower mean heart dose (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.0001), left anterior descending artery V15\u00a0Gy (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.001), mean lung dose (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.008), and effective dose to immune circulating cells (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38\u20130.81; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37\u20130.81; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.003). There was no difference in other G3+ toxicities, progression\u2010free survival, or overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35230","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T12:53:47Z","timestamp":1706705627000},"page":"2031-2041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Acute hospitalizations after proton therapy versus intensity\u2010modulated radiotherapy for locally advanced non\u2013small cell lung cancer in the durvalumab era"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6125-0754","authenticated-orcid":false,"given":"Michelle","family":"Iocolano","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Yegya\u2010Raman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Friedes","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Kegelman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Delaware Radiation Oncology Associates Christiana Care Health Systems  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Radiation Physics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Cengel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Konski","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Leonard Davis Institute of Health Economics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey J.","family":"Langer","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger B.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lova","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charu","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Doucette","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon\u2010Keng","family":"Kevin Teo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Division of Physics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-3694","authenticated-orcid":false,"suffix":"II","given":"Charles B.","family":"Simone","sequence":"additional","affiliation":[{"name":"New York Proton Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Feigenberg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809697"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.1378"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.0720"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2022.07.017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2020.12.019"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2021.02.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.4889"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13246193"},{"key":"e_1_2_9_10_1","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE). Published online2017."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X211027181"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2023.110030"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2023.110005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.10.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2021.01.022"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.05.064"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.08.047"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.07.1695"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2022.07.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2022.100391"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2020.02.015"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1066255"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.06.020"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctro.2017.09.008"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa182"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S282062"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.14338\/IJPT\u201017\u201000033.1"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2023.08.058"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2022.12.030"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014\u2010016\u20100640\u20108"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.35230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:54:09Z","timestamp":1760266449000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.35230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/cncr.35230"],"URL":"https:\/\/doi.org\/10.1002\/cncr.35230","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,31]]},"assertion":[{"value":"2023-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}