{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:16:09Z","timestamp":1792793769791,"version":"4.5.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"1173","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Medical Research Education"},{"name":"Sheba Medical Center Tel Hashomer Israel","id":[{"id":"https:\/\/ror.org\/020rzx487","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>We hypothesized that pneumonitis during Pacific protocol (PDP) contributes to poor outcomes in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with chemoradiation (ChRT) and durvalumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed cases with LANSCLC extracted from a single academic institution database to identify patient, tumour, and treatment characteristics predicting for development of PDP and its effect on oncologic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our database review identified 119 patients with LANSCLC that were treated with ChRT and durvalumab. Sixty-five percent were male and had a mean age of 66\u2009years (SD 8); 58% stage IIB-IIIA, and 51% adenocarcinoma. PDP occurred in 35 (29.4%) cases, at a mean 2.6\u2009months from durvalumab initiation (range 0.3-11\u2009months), and was mostly low grade: G1-12, G2-18, G3-3, G4-1, G5-1. PDP resulted in treatment interruption in 24 cases (20%) with treatment discontinuation in 17 cases (14.3%). Multivariate analysis (MVA) showed all-grades PDP correlated with tumour stage, ipsilateral lung V5\u2009\u2265\u200970%, and mean heart dose (MHD) \u2265 6\u2009Gy. Grades 2-5 PDP correlated with total lungs V20\u2009\u2265\u200927% and MHD \u2265 6\u2009Gy. PDP did not correlate with a history of prior radiation pneumonitis (RP) (9\/119). PDP was associated with decreased 3-year local control (LC) and progression-free survival (PFS); LC 53% vs 75.5% (HR 2.15, P\u2009=\u20090.031); PFS 35.5% vs 56.5% (HR 1.8, P\u2009=\u20090.04); and a trend for shorter overall survival (OS; 66% vs 77.5%, HR 1.5, P\u2009=\u20090.27).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PDP correlated with ipsilateral lung V5\u2009\u2265\u200970%, lungs V20\u2009\u2265\u200927% and MHD \u2265 6\u2009Gy. PDP was associated with inferior LC and PFS and trended for shorter OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Advances in knowledge<\/jats:title>\n                    <jats:p>PDP occurred in a third of patients resulting in treatment discontinuation in 14.3%. PDP grades 2-5 correlated with radiation dose to lungs V20\u2009\u2265\u200927% and MHD \u2265 6\u2009Gy. PDP was associated with inferior LC and PFS and trended for shorter OS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjr\/tqaf133","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T12:03:42Z","timestamp":1751025822000},"page":"1436-1445","source":"Crossref","is-referenced-by-count":4,"title":["Pneumonitis after chemoradiation followed by durvalumab for locally advanced lung cancer: predictors and effect on survival"],"prefix":"10.1093","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4235-5075","authenticated-orcid":false,"given":"Sarit","family":"Appel","sequence":"first","affiliation":[{"name":"The Benjamin Davidai Department of Radiation Oncology, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]},{"name":"Arrow Program for Medical Research Education, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Wilk","sequence":"additional","affiliation":[{"name":"Arrow Program for Medical Research Education, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram","family":"Saad","sequence":"additional","affiliation":[{"name":"Jusidman Cancer Center, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Urban","sequence":"additional","affiliation":[{"name":"Jusidman Cancer Center, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Sorotsky","sequence":"additional","affiliation":[{"name":"Jusidman Cancer Center, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Kalmanovitz","sequence":"additional","affiliation":[{"name":"Jusidman Cancer Center, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Onn","sequence":"additional","affiliation":[{"name":"Jusidman Cancer Center, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]},{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, 69978,","place":["Israel"]},{"name":"Department of Pulmonology, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ory","family":"Haisraely","sequence":"additional","affiliation":[{"name":"The Benjamin Davidai Department of Radiation Oncology, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith M","family":"Marom","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, 69978,","place":["Israel"]},{"name":"Diagnostic Radiology Department, Sheba Medical Center , Ramat Gan, 5262160,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaacov R","family":"Lawrence","sequence":"additional","affiliation":[{"name":"The Benjamin Davidai Department of Radiation Oncology, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]},{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, 69978,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Sourasky Medical Center Tel Aviv , Tel Aviv, 6423906,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jair","family":"Bar","sequence":"additional","affiliation":[{"name":"Jusidman Cancer Center, Sheba Medical Center Tel Hashomer , Ramat Gan, 5262160,","place":["Israel"]},{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, 69978,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"2025123019064010700_tqaf133-B1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13014-021-01979-z","article-title":"Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer","volume":"17","author":"Mayahara","year":"2022","journal-title":"Radiat Oncol"},{"key":"2025123019064010700_tqaf133-B2","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.ijrobp.2023.09.050","article-title":"Pneumonitis after chemoradiotherapy and adjuvant durvalumab in stage III non-small cell lung cancer","volume":"118","author":"Edwards","year":"2024","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025123019064010700_tqaf133-B3","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.ijrobp.2012.04.043","article-title":"Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis","volume":"85","author":"Palma","year":"2013","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025123019064010700_tqaf133-B4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0360-3016(99)00183-2","article-title":"Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC)","volume":"45","author":"Graham","year":"1999","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025123019064010700_tqaf133-B5","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.3109\/0284186X.2015.1061216","article-title":"New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy","volume":"54","author":"Khalil","year":"2015","journal-title":"Acta Oncol"},{"key":"2025123019064010700_tqaf133-B6","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/1748-717X-9-172","article-title":"Risk and predictors for early radiation pneumonitis in patients with stage III non-small cell lung cancer treated with concurrent or sequential chemoradiotherapy","volume":"9","author":"Dang","year":"2014","journal-title":"Radiat Oncol"},{"key":"2025123019064010700_tqaf133-B7","doi-asserted-by":"crossref","first-page":"101130","DOI":"10.1016\/j.adro.2022.101130","article-title":"Predictors of pneumonitis in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiation followed by consolidative durvalumab","volume":"8","author":"Diamond","year":"2023","journal-title":"Adv Radiat Oncol"},{"key":"2025123019064010700_tqaf133-B8","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1056\/NEJMoa1709937","article-title":"Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","volume":"377","author":"Antonia","year":"2017","journal-title":"N Engl J Med"},{"key":"2025123019064010700_tqaf133-B9","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1200\/JCO.21.01308","article-title":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","volume":"40","author":"Spigel","year":"2022","journal-title":"J Clin Oncol"},{"key":"2025123019064010700_tqaf133-B10","author":"Network NCC","year":"2024"},{"key":"2025123019064010700_tqaf133-B11","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.lungcan.2022.02.003","article-title":"Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: a post-hoc analysis of the PACIFIC trial","volume":"166","author":"Naidoo","year":"2022","journal-title":"Lung Cancer"},{"key":"2025123019064010700_tqaf133-B12","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1111\/1759-7714.14452","article-title":"Chemoradiation followed by adjuvant durvalumab in stage III non-small cell lung cancer: real-world comparison of treatment outcomes to historical controls treated with chemoradiation alone","volume":"13","author":"Saad","year":"2022","journal-title":"Thorac Cancer"},{"key":"2025123019064010700_tqaf133-B13","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/j.jtho.2018.08.2035","article-title":"Pneumonitis in non-small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors","volume":"13","author":"Suresh","year":"2018","journal-title":"J Thorac Oncol"},{"key":"2025123019064010700_tqaf133-B14","first-page":"1783","article-title":"Association of immune-related adverse events with durvalumab efficacy after chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer","volume-title":"Br J cancer","author":"Haratani","year":"2024"},{"key":"2025123019064010700_tqaf133-B15","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1038\/s41467-023-39874-8","article-title":"Impact of TMB\/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC","volume":"14","author":"Alessi","year":"2023","journal-title":"Nat Commun"},{"key":"2025123019064010700_tqaf133-B16","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20180960","article-title":"Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes","volume":"92.","author":"Appel","year":"2019","journal-title":"The British Journal of Radiology"},{"key":"2025123019064010700_tqaf133-B17","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ijrobp.2015.06.011","article-title":"Continuous positive airway pressure for motion management in stereotactic body radiation therapy to the lung: a controlled pilot study","volume":"93","author":"Goldstein","year":"2015","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025123019064010700_tqaf133-B18","doi-asserted-by":"crossref","first-page":"20190743","DOI":"10.1259\/bjr.20190743","article-title":"Image-guidance triggered adaptive replanning of radiation therapy for locally advanced lung cancer: an evaluation of cases requiring plan adaptation","volume":"93","author":"Appel","year":"2020","journal-title":"Br J Radiol"},{"key":"2025123019064010700_tqaf133-B19","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ad.2019.05.009","article-title":"Using the common terminology criteria for adverse events (CTCAE\u2014version 5.0) to evaluate the severity of adverse events of anticancer therapies","volume":"112","author":"Freites-Martinez","year":"2021","journal-title":"Actas Dermo-Sifiliograficas"},{"key":"2025123019064010700_tqaf133-B20","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1159\/000534376","article-title":"Chemoradiotherapy combined with immunotherapy in stage III non-small cell lung cancer: a systematic review and Meta-Analysis of efficacy and safety outcomes","volume":"102","author":"Li","year":"2024","journal-title":"Oncology"},{"key":"2025123019064010700_tqaf133-B21","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.ijrobp.2021.12.150","article-title":"Real-world safety and efficacy of consolidation durvalumab after chemoradiation therapy for stage III non-small cell lung cancer: a systematic review and meta-analysis","volume":"112","author":"Wang","year":"2022","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025123019064010700_tqaf133-B22","doi-asserted-by":"publisher","first-page":"3713","DOI":"10.1002\/cncr.34915","article-title":"Safety and efficacy of durvalumab after concurrent chemoradiation in black patients with locally advanced non\u2013small cell lung cancer","volume":"129","author":"McCall","year":"2023","journal-title":"Cancer"},{"key":"2025123019064010700_tqaf133-B23","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jtho.2022.07.1148","article-title":"Durvalumab after sequential chemoradiotherapy in stage III, unresectable NSCLC: the phase 2 PACIFIC-6 trial","volume":"17","author":"Garassino","year":"2022","journal-title":"J Thorac Oncol"},{"key":"2025123019064010700_tqaf133-B24","doi-asserted-by":"crossref","first-page":"101315","DOI":"10.1016\/j.adro.2023.101315","article-title":"Adaptive lung radiation therapy in the era of immunotherapy: a single-center retrospective study","volume":"9","author":"Portal","year":"2024","journal-title":"Adv Radiat Oncol"}],"container-title":["British Journal of Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjr\/advance-article-pdf\/doi\/10.1093\/bjr\/tqaf133\/63519199\/tqaf133.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjr\/article-pdf\/98\/1173\/1436\/63519199\/tqaf133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjr\/article-pdf\/98\/1173\/1436\/63519199\/tqaf133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:06:48Z","timestamp":1767139608000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjr\/article\/98\/1173\/1436\/8167887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":24,"journal-issue":{"issue":"1173","published-online":{"date-parts":[[2025,6,18]]},"published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bjr\/tqaf133","relation":{},"ISSN":["0007-1285","1748-880X"],"issn-type":[{"value":"0007-1285","type":"print"},{"value":"1748-880X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,6,18]]}}}