Budesonide versus Placebo in a High-risk Population with Screen-detected Lung Nodules
Figure 4: Subject Characteristics (n=202)
Nodule type
n=138 68%
n=64 32%
n=49 24%
Gender
n=153 76%
Solid
Distribution of maximum nodule diameters (mm)
n=3 1%
n=69 34%
n=130 65%
n=35 17%
Sub-solid
Male
Female
Smoking status
n=167 83%
4–5
5–8
>8
homogenous calcifications, solid nodules with regular and round or polygonal margins and distance from the pleura <1cm), subjects currently suffering from malignant disease or having had malignant disease within the last five years and regular/chronic users of oral or inhaled corticosteroids.
End-points
The primary end-point of the study was the response rate in target nodules in a per-person specific analysis. Secondary end-points included the evaluation of per-lesion analysis by application of Response Evaluation Criteria In Solid Tumors (RECIST) criteria and the average decrease in size of the target lesions, the modulation of biological markers of lung cancer in serum and sputum after treatment (aberrant promoter methylation of retinoic acid receptor beta [RARβ], p16 and RASSF1A genes, ultrasensitive C-reactive protein) and the correlation of these findings with modification of lung nodule sizes. The toxicity of budesonide was also assessed in this cohort of subjects; in addition, since a link between lung cancer and COPD has been documented,24
we evaluated the effect of budesonide
on COPD by both spirometry and spiral CT. The effect of inhaled budesonide on respiratory function was studied by comparison of pulmonary function tests (PFTs), diffusing capacity of the lung for
carbon monoxide (DLCO) and oxygen saturation (SaO2) before and after one year of treatment; the role of the CT scan in estimating the grade of respiratory impairment and emphysema was analysed by comparing it with PFTs and symptoms.
Patient Characteristics
Among the 4,821 subjects who underwent the second annual low- dose CT screening in the COSMOS study, a total of 527 subjects were screened for protocol inclusion given the presence of persistent undetermined nodules at second CT, and 392 were eligible according to nodule characteristics. Two hundred and two were randomised
EUROPEAN ONCOLOGY
Current
Former
Figure 5: Accrual – April 2006 to July 2007
120 160 200
40 80
0 1 2 34 5 6 78 9 10
Months of enrolment Goal
11 Actual
from April 2006 to July 2007; 101 participants were allocated to each study arm. The characteristics of the participants are shown in Figure 4. There was no statistically significant difference in median age, sex, smoking history, type of nodule, size of nodule and risk assessment for lung cancer. Overall, 198 subjects completed the 12-month study and were included in the analysis. Three subjects were lost to follow-up and one participant withdrew consent to the trial (drop-out rate 2%).
What We Know So Far
Lam’s results are definitely encouraging, but there are some important matters that should be mentioned about the trial. Over 80% of nodules were <4mm, most nodules on low-dose CT were evaluated retrospectively, only three nodules were non-solid type and the vast majority were new nodules, most of which may represent acute inflammation. Thus, the degree of reduction in nodule size obtained
17
12 13 14 15 16
Cumulative enrolment (n)
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100