J J Vehreschild1,2, C P Heussel3,4,5, A H Groll6, M J G T Vehreschild7,8, G Silling9, G Würthwein10, M Brecht3, O A Cornely7,11,12,13. 1. Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. janne.vehreschild@ctuc.de. 2. German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. janne.vehreschild@ctuc.de. 3. Diagnostic and Interventional Radiology with Nuclear Medicine, Chest Clinic at University Hospital Heidelberg, Heidelberg, Germany. 4. Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. 5. Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. 6. Infectious Disease Research Program, Department of Paediatric Haematology/Oncology, University Children's Hospital, Muenster, Germany. 7. Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. 8. German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. 9. Department of Medicine A, Haematology/Oncology, University of Muenster, Muenster, Germany. 10. Centre for Clinical Trials, ZKS Muenster (BMBF 01KN1105), University Hospital Muenster, Muenster, Germany. 11. Clinical Trials Center Cologne, ZKS Koeln (BMBF 01KN1106), University of Cologne, Cologne, Germany. 12. Center for Integrated Oncology CIO KölnBonn, Cologne, Germany. 13. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Abstract
BACKGROUND: Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. METHODS: Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. RESULTS: One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. CONCLUSION: Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. KEY POINTS: • CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. • Predictive capability exceeds galactomannan, blood counts, and lesion count. • Any progression between day 7 and day 14 constitutes a high-risk scenario.
BACKGROUND: Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. METHODS: Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. RESULTS: One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. CONCLUSION: Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. KEY POINTS: • CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. • Predictive capability exceeds galactomannan, blood counts, and lesion count. • Any progression between day 7 and day 14 constitutes a high-risk scenario.
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