Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT.

BACKGROUND: Results of randomized clinical trials (RCTs) are needed to assess the efficacy of lung cancer screening with low-dose chest computed tomography (CT) in reducing lung cancer mortality. We report design and results of enrolment and baseline screening test in the ITALUNG trial, a RCT. METHODS: Invitation letters were sent to subjects of 55-69 years of age clients of 269 general practitioners. Smokers or former smokers of at least 20 pack/years were eligible and after written consent were randomized in an active arm undergoing a low-dose CT annually for 4 years and in a control arm receiving no screening. Management of positive screening test was carried out using follow-up low-dose CT, fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology and fiber optic bronchoscopy. RESULTS: A sample of 3206 eligible subjects was achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in control (n = 1593) and active (n = 1613) arm were balanced for age, gender and smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after randomization. The baseline screening test was positive in 426 (30.3%) of 1406 subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects: 18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle aspirations were performed in 15 lung cancers, with a positive result in 12 (75%) cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung cancers (81%) were treated with surgical resection in 16 subjects. One subject underwent surgery for a benign lesion (5.5% of all surgical resections). CONCLUSIONS: Recruitment by mail of high risk subjects for a lung cancer screening RCT is feasible but not efficient. Results of the baseline screening test in the active arm of the ITALUNG trial are substantially in line with those of RCT and observational studies.

Whole-lung densitometry versus visual assessment of emphysema.

We compared whole-lung densitometry with visual evaluation of pulmonary emphysema. Thirty patients with chronic obstructive pulmonary disease underwent multi-detector CT (150 mAs and 0.75 collimation) with double reconstruction: thick (5-mm) slices with smooth filter for whole-lung densitometry and thin (1 mm) slices with sharp filter for visual assessment (one of every ten slices). Densitometry and visual assessment were performed by three operators each, and the time required for assessment, the inter-observer agreement and the correlation with the results of the diffusion capacity of carbon monoxide (DL(CO)) in the same patients were computed. The average time for densitometry (8.49 +/- 0.13 min) was significantly longer (p < 0.0001) than that for visual evaluation (5.14 +/- 0.11 min). However, the inter-operator agreement ranged between "moderate" to "almost perfect" for densitometry (kappa range 0.58-0.87) and "slight" for visual (kappa = 0.20) assessment. The correlation coefficients of DL(CO) with relative area at -960 and -970 Hounsfield units (HU) (both r = -0.66) and of the first percentile point of lung density (r = 0.66) were slightly stronger than that of the visual score (r = -0.62). Densitometry should be preferred to visual assessment because it enables a more reproducible evaluation of the extent of pulmonary emphysema, which can be carried out on the entire lung in a reasonable amount of time.

Risk factors for development of coronary heart disease in patients with acromegaly: a five-year prospective study.

BACKGROUND: Data on coronary heart disease (CHD) are scanty and matter of argument in acromegalic patients. OBJECTIVE: The objective of this study was to evaluate risk factors for development of CHD and the occurrence of cardiac events in acromegalic patients during a 5-yr prospective study. DESIGN: Ten-year likelihood for CHD development was estimated by the Framingham scoring system (FS); patients were stratified as having low (FS < 10), intermediate (>or= 10 FS < 20), or high (FS >or= 20) risk. Coronary artery calcium content was measured using the Agatston score (AS) in all patients; those with positive AS were submitted to myocardial single-photon emission computed tomography; cardiac events were recorded during a 5-yr follow-up period. PATIENTS: Fifty-two consecutive patients (31 women, mean age 52 +/- 11 yr) with controlled or uncontrolled acromegaly were followed prospectively for 5 yr. RESULTS: Thirty-seven patients (71%) had low, 14 patients (27%) had intermediate, and one patient (2%) had high CHD risk. CHD risk was unrelated to acromegaly activity or the estimated duration of disease. Among patients with FS less than 10%, 24 had AS equal to 0, eight had AS of 1 or greater and less than 100, and five had AS 100 or greater and less than 300, respectively. Among patients with FS 10 or greater and less than 20%, nine had AS equal to 0, two had AS of one or greater and less than 100, one had AS of 100 or greater and less than 300, and two had AS of 300 or greater; a patient of the latter group, having AS of 400 or greater, increased his CHD risk from 11% to 20% or more. FS or AS did not differ in patients with controlled or uncontrolled acromegaly (P = 0.981). All patients with positive AS had no single photon emission computed tomography perfusion defects. During the 5-yr follow-up period no patient developed ischemic cardiac events. CONCLUSIONS: CHD risk in acromegalic patients, predicted by FS as in nonacromegalic subjects, is low; AS might have adjunctive role only in a subset of patients. However, most patients have systemic complications of acromegaly, which participate in the assessment of global CHD risk.