Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis
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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.
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.
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.
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.
• 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.
KeywordsBiomarkers Caspofungin Computed tomography Invasive pulmonary aspergillosis Survival
The scientific guarantor of this publication is Jörg J. Vehreschild (firstname.lastname@example.org)
The authors of this manuscript declare relationships with the following companies:
JJV is supported by the German Federal Ministry of Research and Education (BMBF grant 01KI0771) and the German Centre for Infection Research, has received research grants from Astellas, Gilead Sciences, Infectopharm, Pfizer, and Essex/Schering-Plough; and served on the speakers’ bureau of Astellas, Merck Sharp Dohme/Merck, Gilead Sciences, Pfizer, and Essex/Schering-Plough.
CPH has received research funding from Siemens, Pfizer, MeVis and Boehringer Ingelheim, is a consultant to Schering-Plough, Pfizer, Basilea, Boehringer Ingelheim, Novartis, Roche, Astellas, Gilead, MSD, Lilly, Intermune and Fresenius and has received lecture honoraria from Gilead, Essex, Schering-Plough, AstraZeneca, Lilly, Roche, MSD, Pfizer, Bracco, MEDA Pharma, Intermune, Chiesi, Siemens, Covidien, Pierre Fabre, Boehringer Ingelheim, Grifols and Novartis.
AHG has served on the speaker’s bureau and as a consultant to Astellas Pharma, Cephalon, Gilead Sciences, Merck & Co., Pfizer, Schering-Plough, and Vicuron Pharmaceuticals. He has received research grants from Gilead Sciences, Merck & Co, and Pfizer.
MJGTV has served at the speakers’ bureau of Pfizer, Merck, Gilead Sciences, and Astellas Pharma, received research funding from 3M, Astellas Pharma and Gilead Sciences and is a consultant to Berlin Chemie.
GS has received research funding from MSD Sharp & Dohme, Pfizer, Gilead and Astellas and is a consultant to MSD Sharp & Dohme.
GW has no conflicts of interest to declare.
MB has no conflicts of interest to declare.
OAC is supported by the German Federal Ministry of Research and Education (BMBF grant 01KN1106), has received research grants from 3M, Actelion, Astellas, Basilea, Bayer, Celgene, Cubist, F2G, Genzyme, Gilead, GSK, Merck/MSD, Miltenyi, Optimer, Pfizer, Quintiles, and Viropharma, is a consultant to 3M, Astellas, Basilea, Cubist, F2G, Gilead, GSK, Merck/MSD, Optimer, Pfizer, Sanofi Pasteur and Summit/Vifor, and received lecture honoraria from Astellas, Gilead, Merck/MSD, and Pfizer..
This study has received funding by Merck/MSD.
One of the authors (JJV) has significant statistical expertise.
Institutional Review Board approval was obtained.
Written informed consent was obtained from all subjects (patients) in this study.
The results of the clinical trial were published in Antimicrobial Agents and Chemotherapy: "Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis", doi: 10.1128/AAC.05134-11 (2011)
• randomised controlled trial
• multicenter study
• post-hoc analysis
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