Utility of Computed Tomography for the Diagnosis of Invasive Aspergillosis in Hematological Malignancy

Background: Pulmonary computed tomography (CT) scans are commonly used as part of the clinical criteria in diagnostic workup of invasive aspergillosis (IA). Other criteria for diagnosing IA include a combination of host, clinical and mycological factors, such as those recommended in the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Chest CT criteria include dense, well-circumscribed lesions(s) with or without a halo sign, air-crescent sign, or cavity. We assessed the diagnostic utility of these findings at baseline in a cohort of patients with hematological malignancy and suspected IA who received antifungal treatment.

Material/methods: This post hoc analysis assessed data from a prospective, multicenter international trial of voriconazole (with and without anidulafungin) in patients with suspected (possible, probable, or proven using 2008 EORTC/MSG criteria) IA (NCT00531479). Patients who had received at least one dose of study drug and who had at least one CT scan with a description of 'lung' at baseline were included in this analysis. Patient records as provided by the investigators were retrospectively reviewed in a blinded manner to identify physician notes describing the presence of observable lesions or abnormalities on CT scan at baseline. The presence of IA was subsequently evaluated to confirm the infection. Patients with proven or probable IA were termed 'confirmed' (cIA) and all others as 'non-confirmed' (nIA). This assessment was in accordance with 2008 EORTC/MSG criteria, and conducted by an independent review committee.

Results: Of 395 patients included, 240 patients (60.8%) were classified as cIA and 155 patients (39.2%) as nIA. Baseline characteristics were comparable between cIA and nIA groups: the mean age was 52.3 years vs 50.5 years, 56.3% vs 60.0% were male, and 71.7% vs 71.0% were white, respectively. The most commonly reported CT scan abnormalities at baseline were pulmonary nodules (46.8% of all patients; Table 1), bilateral lung lesions (37.5%), unilateral lung lesions (28.4%), and consolidation (24.8%). Abnormalities associated with subsequent confirmation of IA were ground-glass attenuation (cIA: 24.2%; nIA: 11.6%; p <0.05) and pulmonary nodules (cIA: 52.5%; nIA: 38.1%; p <0.05). Bilateral lung lesions were more common in cIA (41.3%) than in nIA (31.6%) patients, but this did not reach statistical significance (p=0.0561). No other CT scan abnormality appeared to be associated with confirmation of IA.

Conclusions: Generally, chest CT scan abnormalities (including halo signs and air crescent signs) at baseline in patients with hematological malignancy and suspected IA based on the EORTC/MSG criteria were not associated with subsequent confirmation of IA. However, ground-glass attenuation, nodules and, to a lesser degree, bilateral lung lesions were associated with subsequent confirmation of IA. It should be considered that patients with possible IA and abnormal chest CT findings may have had the infection, even if further investigation failed to upgrade the diagnosis to proven/probable; this could result in an underestimation of the discriminative value of chest CT. These findings suggest that chest CT should be interpreted in conjunction with other available clinical data to guide management decisions on individual patients, including whether treatment is reasonable, pending full evaluation. Caution must be taken given this is a post-hoc analysis of a randomized, controlled, prospective trial; further confirmative studies are warranted.

View largeDownload slide

View largeDownload slide

Close modal