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

Sci Transl Med. 2014 Dec 3;6(265):265ra166. doi: 10.1126/scitranslmed.3009501.

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-[(18)F]-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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Double-Blind Method
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Lung / diagnostic imaging
  • Male
  • Metronidazole / therapeutic use
  • Multimodal Imaging
  • Observer Variation
  • Positron-Emission Tomography*
  • Prospective Studies
  • ROC Curve
  • Radiographic Image Interpretation, Computer-Assisted
  • Sensitivity and Specificity
  • Software
  • Sputum / microbiology
  • Tomography, X-Ray Computed*
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / diagnostic imaging*
  • Tuberculosis, Multidrug-Resistant / therapy*

Substances

  • Fluorodeoxyglucose F18
  • Metronidazole