Clinical testing of drug treatment shortening in patients with TB using PET/CT imaging of lung lesions
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Stephanus T Malherbe Ray Y Chen Xiang Yu Bronwyn Smith Xin Liu Jingcai Gao Andreas H Diacon Rodney Dawson Michele Tameris Hong Zhu Yahong Qu Hongjian Jin Shouguo Pan Lori E Dodd Jing Wang Lisa C Goldfeder Ying Cai Kriti Arora Joel Vincent Kim Narunsky Keboile Serole Rene T Goliath Laylah Da Costa Arshad Taliep Saalikha Aziz Remy Daroowala Friedrich Thienemann Sandra Mukasa Richard Court Bianca Sossen Petri Ahlers Simon C Mendelsohn Lisa White Aurélie Gouel Chuen-Yen Lau Samy Hassan Lili Liang Hongfei Duan Gita K Moghaddam Praveen Paripati Saher Lahouar Michael Harris Kurt Wollenberg Brendan Jeffrey Mike Tartakovsky Alex Rosenthal Michael Duvenhage Derek T Armstrong Taeksun Song Jill Winter Qian Gao Laura E Via Robert Wilkinson Gerhard Walzl Clifton E Barry III
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Abstract
Six months of drug treatment is standard of care for drug-sensitive pulmonary tuberculosis (TB). Understanding the factors determining the length of treatment required for durable cure would allow individualization of treatment durations. We conducted a prospective, randomized, controlled noninferiority trial (PredictTB) of 4 versus 6 months of chemotherapy in patients with pulmonary TB in South Africa and China. Seven hundred and four participants with newly diagnosed, drug-sensitive TB were enrolled and stratified on the basis of radiographic disease characteristics assessed by FDG PET/CT imaging. Participants with less extensive disease (n = 273) were randomly assigned at week 16 to complete therapy after 4 months or continue receiving treatment for 6 months. This study was stopped early after an interim analysis revealed that patients assigned to the 4-month treatment arm had a higher risk of relapse. Among participants who received 4 months of chemotherapy, 17 of 141 (12.1%) experienced TB-specific unfavorable outcomes compared with only 2 of 132 (1.5%) who completed 6 months of treatment. In the nonrandomized arm that included participants with more extensive disease, only 8 of 248 (3.2%) experienced unfavorable outcomes. Total lung cavity volume and lesion glycolysis at week 16 were associated with the risk of unfavorable outcomes. PET/CT imaging at TB recurrence showed that bacteriological relapses predominantly occurred in active cavities originally present at baseline. Subsequent post hoc automated segmentation of serial PET/CT scans combined with machine learning enabled the classification of participants according to their likelihood of relapse.
Journal details
Journal
Science Translational Medicine
Volume
18
Issue number
831
Pages
eadt5626
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10.1126/scitranslmed.adt5626
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Europe PubMed Central
41499522
Pubmed
41499522
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The publication was previously a preprint.
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