PMID- 26205737 OWN - NLM STAT- MEDLINE DCOM- 20160621 LR - 20181113 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 20 IP - 9 DP - 2015 Sep TI - Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenstrom Macroglobulinemia as a Paradigm. PG - 1077-83 LID - 10.1634/theoncologist.2015-0033 [doi] AB - BACKGROUND: This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenstrom macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis. MATERIALS AND METHODS: A total of 40 patients (23 men, 17 women; 43-84 years old) with Waldenstrom 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. RESULTS: 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 < .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. CONCLUSION: Drug-related pneumonitis was noted on CT in 58% of Waldenstrom 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. IMPLICATIONS FOR PRACTICE: 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 Waldenstrom 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 Waldenstrom 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. CI - (c)AlphaMed Press. FAU - Nishino, Mizuki AU - Nishino M AD - Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA Mizuki_Nishino@dfci.harvard.edu. FAU - Boswell, Erica N AU - Boswell EN AD - Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA. FAU - Hatabu, Hiroto AU - Hatabu H AD - Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA. FAU - Ghobrial, Irene M AU - Ghobrial IM AD - Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA. FAU - Ramaiya, Nikhil H AU - Ramaiya NH AD - Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA. LA - eng GR - K23 CA157631/CA/NCI NIH HHS/United States GR - 1K23CA157631/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150723 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Protein Kinase Inhibitors) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Humans MH - Male MH - Middle Aged MH - Pneumonia/*chemically induced/*diagnostic imaging MH - Protein Kinase Inhibitors/*adverse effects/therapeutic use MH - Radiography MH - Retrospective Studies MH - Sirolimus/*adverse effects/therapeutic use MH - Waldenstrom Macroglobulinemia/*diagnostic imaging/*drug therapy PMC - PMC4571812 OTO - NOTNLM OT - Computed tomography OT - Drug toxicity OT - Mammalian target of rapamycin inhibitor OT - Pneumonitis OT - Waldenstrom macroglobulinemia OT - mTOR COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2015/07/25 06:00 MHDA- 2016/06/22 06:00 PMCR- 2016/03/01 CRDT- 2015/07/25 06:00 PHST- 2015/01/28 00:00 [received] PHST- 2015/05/01 00:00 [accepted] PHST- 2015/07/25 06:00 [entrez] PHST- 2015/07/25 06:00 [pubmed] PHST- 2016/06/22 06:00 [medline] PHST- 2016/03/01 00:00 [pmc-release] AID - theoncologist.2015-0033 [pii] AID - T1533 [pii] AID - 10.1634/theoncologist.2015-0033 [doi] PST - ppublish SO - Oncologist. 2015 Sep;20(9):1077-83. doi: 10.1634/theoncologist.2015-0033. Epub 2015 Jul 23.