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Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab

Sree Harsha Tirumani, Nikhil H. Ramaiya, Abhishek Keraliya, Nancy D. Bailey, Patrick A. Ott, F. Stephen Hodi and Mizuki Nishino
Sree Harsha Tirumani
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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Nikhil H. Ramaiya
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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Abhishek Keraliya
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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Nancy D. Bailey
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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Patrick A. Ott
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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F. Stephen Hodi
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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Mizuki Nishino
1Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
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  • For correspondence: Mizuki_Nishino@dfci.harvard.edu
DOI: 10.1158/2326-6066.CIR-15-0102 Published October 2015
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    Figure 1.

    The cumulative probability of radiographically evident irAEs during ipilimumab therapy.

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    Figure 2.

    Colitis with a diffuse colitis pattern in a 64-year-old man with advanced melanoma treated with ipilimumab, presenting with diarrhea. Coronal reformatted contrast-enhanced CT image of the abdomen obtained 2.6 months after the initiation of ipilimumab treatment showed a new fluid-filled dilated colon (*) with mucosal hyperemia indicating diffuse colitis. Colonoscopic biopsy confirmed colonic inflammation with mucosal injury consistent with ipilimumab-associated colitis. The patient was treated with oral steroids followed by i.v. infliximab, leading to resolution of the findings on the follow-up scan at 1.8 months after the onset (data not shown).

  • Figure 3.
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    Figure 3.

    Sarcoid-like lymphadenopathy in an asymptomatic 81-year-old man with metastatic melanoma treated with ipilimumab. A, coronal reformatted contrast-enhanced chest CT performed 4.9 months after the initiation of ipilimumab therapy showed new bilateral symmetric mediastinal and hilar lymphadenopathy, resembling sarcoidosis. B, axial CT image of the lungs showed bilateral irregular and nodular parenchymal opacities in upper and middle lung predominance (arrows), with peribronchovascular involvement, which falls in the spectrum of lung parenchymal manifestations of pulmonary sarcoidosis.

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    Figure 4.

    Sarcoid-like lymphadenopathy in an asymptomatic 55-year-old woman with metastatic melanoma treated with ipilimumab. Axial fused FDG-PET/CT images at 3 months of ipilimumab therapy show new FDG-avid mediastinal and bilateral hilar lymphadenopathy (arrows) mimicking sarcoidosis. A follow-up PET/CT performed 5 months later showed resolution of FDG-avid lymphadenopathy (data not shown).

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    Figure 5.

    Pneumonitis in a 72-year-old woman with metastatic melanoma treated with ipilimumab. Axial CT image of the chest obtained 4.0 months after the initiation of ipilimumab therapy shows new bilateral consolidative and ground glass opacities predominantly in peripheral and lower distribution (arrows), mimicking the COP pattern. The patient was symptomatic with cough at this time and was treated with oral steroids. A further follow-up CT scan performed 2.1 months after the onset showed resolution of the findings (data not shown).

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    Figure 6.

    Hepatitis in a 63-year-old man with metastatic melanoma treated with ipilimumab. Axial contrast-enhanced CT scan of the abdomen performed at 2.7 months of ipilimumab therapy shows new periportal edema (arrows) with hepatomegaly and new periportal lymphadenopathy (arrowhead). Markedly elevated liver functions were noted, leading to liver biopsy, which revealed severe panlobular hepatitis with lymphoplasmacytic infiltrate and eosinophils, and foci of central vein damage and perivenular collapse, consistent with ipilimumab-associated hepatitis. The patient was treated with steroids and mycophenolate, and liver functions were normalized.

Tables

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  • Table 1.

    Demographics and clinical characteristics

    CharacteristicsWith irAE (n = 46)Without irAE (n = 101)Total (N = 147)P
    Sex
     Male2563880.37
     Female213859
    Median age (years)65.064.064.50.81
    Race
     White43851280.18
     Nonwhite31619
    Smoking
     Never2247690.92
     Former224769
     Current279
    ECOG performance status
     033711040.24
     192534
     2314
    Unknown145
    Median duration of ipilimumab therapy (months)8.98.08.10.61
  • Table 2.

    Organ-specific irAEs and the clinical characteristics

    Patients, n (%)Months since therapy initiation, median (range)a
    Colitis (total)28 (19)1.9 (0.4–4.7)
    Sarcoid-like lymphadenopathy8b (5)3.2 (0.2–9.1)
    Pneumonitis8c (5)2.3 (1.1 – 8.3)
    Hepatitis3 (2)1.4 (0.3–2.7)
    Thyroiditis2 (1)4.3 (4.0–4.7)
    Pancreatitis1 (0.6)3.8 (3.8)
    • ↵aMedian and range represent those among the patients who had the events.

    • ↵bIncludes 1 patient who also had colitis.

    • ↵cIncludes 3 patients who also had colitis.

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Cancer Immunology Research: 3 (10)
October 2015
Volume 3, Issue 10
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Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab
Sree Harsha Tirumani, Nikhil H. Ramaiya, Abhishek Keraliya, Nancy D. Bailey, Patrick A. Ott, F. Stephen Hodi and Mizuki Nishino
Cancer Immunol Res October 1 2015 (3) (10) 1185-1192; DOI: 10.1158/2326-6066.CIR-15-0102

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Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab
Sree Harsha Tirumani, Nikhil H. Ramaiya, Abhishek Keraliya, Nancy D. Bailey, Patrick A. Ott, F. Stephen Hodi and Mizuki Nishino
Cancer Immunol Res October 1 2015 (3) (10) 1185-1192; DOI: 10.1158/2326-6066.CIR-15-0102
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