Waxing and waning pattern of mTOR inhibitor-associated pneumonitis in renal cell carcinoma patients: A retrospective observational study

Published:November 04, 2020DOI:


      • One-half of our patients on mTOR inhibitors developed pneumonitis (52%).
      • Of those with pneumonitis, two-thirds had a waxing and waning pattern.



      mTOR inhibitor-associated pneumonitis is common and often asymptomatic. We describe a waxing and waning pattern of pneumonitis observed on computed tomography (CT) scans of patients with renal cell carcinoma who were being treated with mTOR inhibitor molecular targeted therapy.

      Materials and methods

      In this HIPAA-compliant, IRB-approved retrospective single-institution study, 25 renal cell carcinoma patients were identified who received single-therapy temsirolimus or everolimus between January 2011 and June 2015 and who had chest CT scans available for review both before and after initiation of mTOR inhibitor treatment. A detailed review of the electronic medical record and serial chest CT examinations was performed.


      Radiologic findings compatible with pneumonitis were identified in 13/25 (52%) patients on mTOR inhibitors in our study. Of the patients with CT findings of pneumonitis, 8/13 (62%) demonstrated a waxing and waning pattern; of whom 7 had clinical symptoms of pneumonitis. Of the 17 patients who received temsirolimus, 9/17 (53%) developed radiologic findings compatible with pneumonitis and 4/9 (44%) developed a waxing and waning pattern. Of the 8 patients who received everolimus, 4/8 (50%) had radiologic findings compatible with pneumonitis and 4/4 (100%) developed a waxing and waning pattern.


      Waxing and waning is an unrecognized pattern of mTOR inhibitor-associated pneumonitis. Recognition of this pattern will promote clinical-radiologic concordance and may facilitate patient management.


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        • Voss M.H.
        • Molina A.M.
        • Motzer R.J.
        mTOR inhibitors in advanced renal cell carcinoma.
        Hematol Oncol Clin North Am. 2011; 25: 835-852
        • Faes S.
        • Santoro T.
        • Demartines N.
        • Dormond O.
        Evolving significance and future relevance of anti-angiogenic activity of mTOR inhibitors in cancer therapy.
        Cancers. 2017; 9
        • Xie J.
        • Wang X.
        • Proud C.G.
        mTOR inhibitors in cancer therapy.
        F1000Research. 2016; 5
        • Gomez-Pinillos A.
        • Ferrari A.C.
        mTOR signaling pathway and mTOR inhibitors in cancer therapy.
        Hematol Oncol Clin North Am. 2012; 26 ([vii]): 483-505
        • Peddi P.F.
        • Shatsky R.A.
        • Hurvitz S.A.
        Noninfectious pneumonitis with the use of mTOR inhibitors in breast cancer.
        Cancer Treat Rev. 2014; 40: 320-326
        • Duran I.
        • Siu L.L.
        • Oza A.M.
        • Chung T.B.
        • Sturgeon J.
        • Townsley C.A.
        • et al.
        Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus.
        European Journal of Cancer (Oxford, England: 1990). 2006; 42: 1875-1880
        • White D.A.
        • Schwartz L.H.
        • Dimitrijevic S.
        • Scala L.D.
        • Hayes W.
        • Gross S.H.
        Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001).
        J Thorac Oncol. 2009; 4: 1357-1363
        • White D.A.
        • Camus P.
        • Endo M.
        • Escudier B.
        • Calvo E.
        • Akaza H.
        • et al.
        Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma.
        Am J Respir Crit Care Med. 2010; 182: 396-403
        • Maroto J.P.
        • Hudes G.
        • Dutcher J.P.
        • Logan T.F.
        • White C.S.
        • Krygowski M.
        • et al.
        Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus.
        J Clin Oncol. 2011; 29: 1750-1756
        • Atkinson B.J.
        • Cauley D.H.
        • Ng C.
        • Millikan R.E.
        • Xiao L.
        • Corn P.
        • et al.
        Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes.
        BJU Int. 2014; 113: 376-382
        • Nozawa M.
        • Ohzeki T.
        • Tamada S.
        • Hongo F.
        • Anai S.
        • Fujimoto K.
        • et al.
        Differences in adverse event profiles between everolimus and temsirolimus and the risk factors for non-infectious pneumonitis in advanced renal cell carcinoma.
        Int J Clin Oncol. 2015; 20: 790-795
        • Willemsen A.E.
        • Grutters J.C.
        • Gerritsen W.R.
        • van Erp N.P.
        • van Herpen C.M.
        • Tol J.
        mTOR inhibitor-induced interstitial lung disease in cancer patients: comprehensive review and a practical management algorithm.
        Int J Cancer. 2016; 138: 2312-2321
        • Almeida F.
        • Amorim S.
        • Sarmento A.
        • Santos L.
        Life-threatening everolimus-associated pneumonitis: a case report and a review of the literature.
        Transplant Proc. 2018; 50: 933-938
        • Alvarez R.H.
        • Bechara R.I.
        • Naughton M.J.
        • Adachi J.A.
        • Reuben J.M.
        Emerging perspectives on mTOR inhibitor-associated pneumonitis in breast cancer.
        Oncologist. 2018; 23: 660-669
        • Baselga J.
        • Campone M.
        • Piccart M.
        • Burris 3rd, H.A.
        • Rugo H.S.
        • Sahmoud T.
        • et al.
        Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.
        N Engl J Med. 2012; 366: 520-529
        • Nishino M.
        • Brais L.K.
        • Brooks N.V.
        • Hatabu H.
        • Kulke M.H.
        • Ramaiya N.H.
        Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach.
        Eur J Cancer. 2016; 53: 163-170