PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis

Ray Y. Chen, Lori E. Dodd, Myungsun Lee, Praveen Paripati, Dima A. Hammoud, James M. Mountz, Doosoo Jeon, Nadeem Zia, Homeira Zahiri, M. Teresa Coleman, Matthew W. Carroll, Jong Doo Lee, Yeon Joo Jeong, Peter Herscovitch, Saher Lahouar, Michael Tartakovsky, Alexander Rosenthal, Sandeep Somaiyya, Soyoung Lee, Lisa C. GoldfederYing Cai, Laura E. Via, Seung Kyu Park, Sangnae Cho, Clifton E. Barry

Research output: Contribution to journalArticle

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Abstract

Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.

Original languageEnglish
Article number265ra166
JournalScience Translational Medicine
Volume6
Issue number265
DOIs
Publication statusPublished - 2014 Dec 3

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Multidrug-Resistant Tuberculosis
Tuberculosis
Microbiology
Sputum
Biomarkers
Clinical Trials
Fluorodeoxyglucose F18
Therapeutics
Treatment Failure
Pharmaceutical Preparations
Software
Recurrence
Drug Therapy
Sensitivity and Specificity
Positron Emission Tomography Computed Tomography
Radiologists

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Chen, R. Y., Dodd, L. E., Lee, M., Paripati, P., Hammoud, D. A., Mountz, J. M., ... Barry, C. E. (2014). PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis. Science Translational Medicine, 6(265), [265ra166]. https://doi.org/10.1126/scitranslmed.3009501
Chen, Ray Y. ; Dodd, Lori E. ; Lee, Myungsun ; Paripati, Praveen ; Hammoud, Dima A. ; Mountz, James M. ; Jeon, Doosoo ; Zia, Nadeem ; Zahiri, Homeira ; Coleman, M. Teresa ; Carroll, Matthew W. ; Lee, Jong Doo ; Jeong, Yeon Joo ; Herscovitch, Peter ; Lahouar, Saher ; Tartakovsky, Michael ; Rosenthal, Alexander ; Somaiyya, Sandeep ; Lee, Soyoung ; Goldfeder, Lisa C. ; Cai, Ying ; Via, Laura E. ; Park, Seung Kyu ; Cho, Sangnae ; Barry, Clifton E. / PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis. In: Science Translational Medicine. 2014 ; Vol. 6, No. 265.
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Chen, RY, Dodd, LE, Lee, M, Paripati, P, Hammoud, DA, Mountz, JM, Jeon, D, Zia, N, Zahiri, H, Coleman, MT, Carroll, MW, Lee, JD, Jeong, YJ, Herscovitch, P, Lahouar, S, Tartakovsky, M, Rosenthal, A, Somaiyya, S, Lee, S, Goldfeder, LC, Cai, Y, Via, LE, Park, SK, Cho, S & Barry, CE 2014, 'PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis', Science Translational Medicine, vol. 6, no. 265, 265ra166. https://doi.org/10.1126/scitranslmed.3009501

PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis. / Chen, Ray Y.; Dodd, Lori E.; Lee, Myungsun; Paripati, Praveen; Hammoud, Dima A.; Mountz, James M.; Jeon, Doosoo; Zia, Nadeem; Zahiri, Homeira; Coleman, M. Teresa; Carroll, Matthew W.; Lee, Jong Doo; Jeong, Yeon Joo; Herscovitch, Peter; Lahouar, Saher; Tartakovsky, Michael; Rosenthal, Alexander; Somaiyya, Sandeep; Lee, Soyoung; Goldfeder, Lisa C.; Cai, Ying; Via, Laura E.; Park, Seung Kyu; Cho, Sangnae; Barry, Clifton E.

In: Science Translational Medicine, Vol. 6, No. 265, 265ra166, 03.12.2014.

Research output: Contribution to journalArticle

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T1 - PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis

AU - Chen, Ray Y.

AU - Dodd, Lori E.

AU - Lee, Myungsun

AU - Paripati, Praveen

AU - Hammoud, Dima A.

AU - Mountz, James M.

AU - Jeon, Doosoo

AU - Zia, Nadeem

AU - Zahiri, Homeira

AU - Coleman, M. Teresa

AU - Carroll, Matthew W.

AU - Lee, Jong Doo

AU - Jeong, Yeon Joo

AU - Herscovitch, Peter

AU - Lahouar, Saher

AU - Tartakovsky, Michael

AU - Rosenthal, Alexander

AU - Somaiyya, Sandeep

AU - Lee, Soyoung

AU - Goldfeder, Lisa C.

AU - Cai, Ying

AU - Via, Laura E.

AU - Park, Seung Kyu

AU - Cho, Sangnae

AU - Barry, Clifton E.

PY - 2014/12/3

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N2 - Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.

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