{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T21:40:59Z","timestamp":1771623659894,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T00:00:00Z","timestamp":1437609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1K23CA157631"],"award-info":[{"award-number":["1K23CA157631"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background.<\/jats:title>\n                  <jats:p>This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenstr\u00f6m macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods.<\/jats:title>\n                  <jats:p>A total of 40 patients (23 men, 17 women; 43\u201384 years old) with Waldenstr\u00f6m macroglobulinemia treated in 2 trials of the mTOR inhibitor everolimus were retrospectively studied. Chest computed tomography (CT) scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by the consensus of three radiologists, evaluating the extent, distributions, and specific findings. The radiographic patterns of pneumonitis were classified using the American Thoracic Society\/European Respiratory Society classification of interstitial pneumonia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results.<\/jats:title>\n                  <jats:p>Drug-related pneumonitis was noted in 23 patients (58%). The median time from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower lungs were involved in all 23 patients, with a higher extent than in the other zones (p &amp;lt; .001). The distribution was peripheral and lower in 11 patients (48%) and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients (87%). Ground glass opacities (GGOs) and reticular opacities were present in all 23 patients, with consolidation in 12, traction bronchiectasis in 2, and centrilobular nodularity in 1. The pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion.<\/jats:title>\n                  <jats:p>Drug-related pneumonitis was noted on CT in 58% of Waldenstr\u00f6m macroglobulinemia patients treated with mTOR inhibitor therapy. Most common findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice:<\/jats:title>\n                  <jats:p>The present study has demonstrated that drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy is highly frequent, occurring in 58% of patients with Waldenstr\u00f6m macroglobulinemia. The radiographic patterns of pneumonitis demonstrated cryptogenic organizing pneumonia and nonspecific interstitial pneumonia patterns, with overlapping features in 30% of the patients. The present study describes an initial attempt of a radiographic pattern-based approach to drug-related pneumonitis in the era of molecular targeting therapy, with a cohort of patients with Waldenstr\u00f6m macroglobulinemia receiving mTOR inhibitor therapy as a paradigm, which might contribute to further understanding and in-depth interpretation of lung toxicity during novel cancer therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2015-0033","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T02:29:56Z","timestamp":1437704996000},"page":"1077-1083","source":"Crossref","is-referenced-by-count":50,"title":["Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenstr\u00f6m Macroglobulinemia as a Paradigm"],"prefix":"10.1093","volume":"20","author":[{"given":"Mizuki","family":"Nishino","sequence":"first","affiliation":[{"name":"Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute;, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica N.","family":"Boswell","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute;, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroto","family":"Hatabu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute;, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene M.","family":"Ghobrial","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute;, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil H.","family":"Ramaiya","sequence":"additional","affiliation":[{"name":"Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute;, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,7,23]]},"reference":[{"key":"2021122309372971000_B1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0033-8389(03)00109-X","article-title":"High-resolution CT of drug-induced lung disease","volume":"40","author":"Erasmus","year":"2002","journal-title":"Radiol Clin North Am"},{"key":"2021122309372971000_B2","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1200\/JCO.2009.24.0994","article-title":"Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia","volume":"28","author":"Ghobrial","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122309372971000_B3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0140-6736(08)61039-9","article-title":"Efficacy of everolimus in advanced renal cell carcinoma: A double-blind, randomised, placebo-controlled phase III trial","volume":"372","author":"Motzer","year":"2008","journal-title":"Lancet"},{"key":"2021122309372971000_B4","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa066838","article-title":"Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma","volume":"356","author":"Hudes","year":"2007","journal-title":"N Engl J Med"},{"key":"2021122309372971000_B5","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.1200\/JCO.2005.13.466","article-title":"Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma","volume":"23","author":"Witzig","year":"2005","journal-title":"J Clin Oncol"},{"key":"2021122309372971000_B6","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S1470-2045(11)70062-6","article-title":"Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: A phase 2 study","volume":"12","author":"Ansell","year":"2011","journal-title":"Lancet Oncol"},{"issue":"suppl 2","key":"2021122309372971000_B7","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/CCO.0b013e32835de8ee","article-title":"Temsirolimus in the treatment of mantle cell lymphoma: Frequency and management of adverse effects","volume":"25","author":"Bouabdallah","year":"2013","journal-title":"Curr Opin Oncol"},{"key":"2021122309372971000_B8","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.3109\/0284186X.2013.770166","article-title":"mTOR inhibitor-related pulmonary toxicity; 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