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Thoracic Imaging of Solid Tumor Patients Treated with Immune Checkpoint Inhibitors

  • Chest Imaging (T Henry, Section Editor)
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Abstract

Purpose of Review

Immune checkpoint inhibitors harness the patient’s own immune system to fight cancer. They are now approved for treating a number of solid malignancies, with more agents and indications expected in the coming months and years. Because of their unique mechanism of action, these agents may lead to unusual imaging appearances.

Recent Findings

Rare patients may experience pseudoprogression, whereby tumors may initially increase in size or number despite response to therapy. Many patients will experience autoimmune side effects including pneumonitis, which may lead to respiratory compromise and will necessitate cessation of therapy. Occasionally pneumonitis or a sarcoid-like reaction can mimic metastatic disease.

Summary

It is imperative that radiologists be aware of these unusual imaging manifestations in patients on immunotherapy so that they are able to assist oncologists in appropriately treating these patients. In particular, we urge caution in interpreting new or enlarging lesions, since these may not always mean progression of disease. Additionally, radiologists should look out for potential immune-related side effects of these therapies.

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References

Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. Jensen P, Hansen S, Møller B, Leivestad T, Pfeffer P, Geiran O, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177–86.

    Article  CAS  PubMed  Google Scholar 

  2. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol. 2016;34:539–73.

    Article  CAS  PubMed  Google Scholar 

  4. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44:989–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hoos A, Eggermont AMM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, et al. Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst. 2010;102:1388–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33:1889–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med. 2015;373:1627–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.

    Article  PubMed  Google Scholar 

  11. Diggs LP, Hsueh EC. Utility of PD-L1 immunohistochemistry assays for predicting PD-1/PD-L1 inhibitor response. Biomark Res. 2017;5:12.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–20.

    Article  CAS  PubMed  Google Scholar 

  13. Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26:2375–91.

    CAS  PubMed  Google Scholar 

  14. Wang GX, Guo LQ, Gainor JF, Fintelmann FJ. Immune checkpoint inhibitors in lung cancer: imaging considerations. Am J Roentgenol. 2017;209:567–75.

    Article  Google Scholar 

  15. •• Kwak JJ, Tirumani SH, Van den Abbeele AD, Koo PJ, Jacene HA. Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events. RadioGraphics. 2015;35:424–37. This article provides a nice imaging-based overview of how to evaluate patients being treated with immune checkpoint inhibitors. It shows examples of pseudoprogression, sarcoid-like reaction, and pneumonitis, as well as many extrathoracic immune-related adverse events.

  16. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  17. Nishino M, Gargano M, Suda M, Ramaiya NH, Hodi FS. Optimizing immune-related tumor response assessment: does reducing the number of lesions impact response assessment in melanoma patients treated with ipilimumab? J Immunother Cancer. 2014;2:17.

    Article  PubMed  PubMed Central  Google Scholar 

  18. • Hodi FS, Hwu W-J, Kefford R, Weber JS, Daud A, Hamid O, et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab. J Clin Oncol. 2016;JCO640391. This article shows the importance of using the immune-related response criteria instead of standard RECIST, as the latter would overestimate progression.

  19. Henze J, Maintz D, Persigehl T. RECIST 1.1, irRECIST 1.1, and mRECIST: how to do. Curr Radiol Rep. 2016;4:48.

    Article  Google Scholar 

  20. •• Tirkes T, Hollar MA, Tann M, Kohli MD, Akisik F, Sandrasegaran K. Response Criteria in oncologic imaging: review of traditional and new criteria. RadioGraphics. 2013;33:1323–41. This article provides an excellent overview of a number of different tumor response criteria, including RECIST 1.1 and irRC.

  21. Chowdhury FU, Sheerin F, Bradley KM, Gleeson FV. Sarcoid-like reaction to malignancy on whole-body integrated 18F-FDG PET/CT: prevalence and disease pattern. Clin Radiol. 2009;64:675–81.

    Article  CAS  PubMed  Google Scholar 

  22. Inoue K, Goto R, Shimomura H, Fukuda H. FDG-PET/CT of sarcoidosis and sarcoid reactions following antineoplastic treatment. SpringerPlus. 2013;2:113.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Osta BE, Hu F, Sadek R, Chintalapally R, Tang S-C. Not all immune-checkpoint inhibitors are created equal: meta-analysis and systematic review of immune-related adverse events in cancer trials. Crit Rev Oncol Hematol. 2017;119:1–12.

    Article  PubMed  Google Scholar 

  24. de Filette J, Jansen Y, Schreuer M, Everaert H, Velkeniers B, Neyns B, et al. Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab. J Clin Endocrinol Metab. 2016;101:4431–9.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Weber JS, Yang JC, Atkins MB, Disis ML. Toxicities of immunotherapy for the practitioner. J Clin Oncol. 2015;33:2092–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Heinzerling L, Ott PA, Hodi FS, Husain AN, Tajmir-Riahi A, Tawbi H, et al. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer. 2016;4:50.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375:1749–55.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dasanu CA, Jen T, Skulski R. Late-onset pericardial tamponade, bilateral pleural effusions and recurrent immune monoarthritis induced by ipilimumab use for metastatic melanoma. J Oncol Pharm Pract. 2017;23:231–4.

    Article  PubMed  Google Scholar 

  29. Yun S, Vincelette ND, Mansour I, Hariri D, Motamed S. Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication. Case Rep Oncol Med. 2015. https://www.hindawi.com/journals/crionm/2015/794842/. Accessed from 20 Sept 2017.

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Authors and Affiliations

  1. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Mark M. Hammer

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  1. Mark M. Hammer
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Correspondence to Mark M. Hammer.

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Mark M. Hammer declares no potential conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical collection on Chest Imaging.

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Hammer, M.M. Thoracic Imaging of Solid Tumor Patients Treated with Immune Checkpoint Inhibitors. Curr Radiol Rep 6, 8 (2018). https://doi.org/10.1007/s40134-018-0269-5

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  • DOI: https://doi.org/10.1007/s40134-018-0269-5

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