Lung Cancer Screening in People With COPD: The Pamplona-IELCAP Experience.

INTRODUCTION: The Global Initiative for Obstructive Lung Disease (GOLD) recommends lung cancer screening for patients with Chronic Obstructive Pulmonary Disease (COPD), but data is lacking regarding results of screening in this high-risk population. The main goal of the present work is to explore if lung cancer screening with Low Dose Chest Tomography (LDCT) in people with COPD, allows lung cancer (LC) diagnosis in early stages with survival compatible with curative state. METHODS: This is a post hoc exploratory analysis. Pamplona International Early Lung Cancer Action Program (P-IELCAP) participants with a GOLD defined obstructive pattern (post bronchodilator FEV1/FVC<0.70) were selected for analysis. The characteristics of those who developed LC and their survival are described. A Cox proportional analysis explored the factors associated with LC diagnosis. RESULTS: Eight hundred and sixty-five patients (77% male, 93% in spirometric GOLD stage 1+2) were followed for 102±63 months. LC prevalence was 2.6% at baseline, with an annual LC diagnosis rate of 0.68%. Early-stage tumors predominated (74%) with a median survival (25-75th percentiles) of 139 (76-185) months. Cumulative tobacco exposure, FEV1%, and emphysema were the main predictors of an LC diagnosis. Eight (11%) patients with COPD had a second LC, most of them in early stage (92%), and 6 (8%) had recurrence. Median survival (25-75th percentiles) in these patients was 168 (108-191) months. CONCLUSIONS: Lung cancer screening of selected high-risk participants with COPD allowed the LC diagnosis in early stages with survival compatible with curative state.

Prevalence and burden of bronchiectasis in a lung cancer screening program.

INTRODUCTION: The prevalence of bronchiectasis in the general population and in individuals undergoing lung cancer screening with low dose computed tomography (LDCT) is unknown. The aim of this study is to estimate the prevalence and impact of bronchiectasis in a screening lung cancer program. METHODS: 3028 individuals participating in an international multicenter lung cancer screening consortium (I-ELCAP) were selected from 2000 to 2012. Patients with bronchiectasis on baseline CT were identified and compared to selected controls. Detection of nodules, need for additional studies and incidence of cancer were analyzed over the follow-up period. RESULTS: The prevalence of bronchiectasis was 11.6%(354/3028). On the baseline LDCT, the number of subjects with nodules identified was 189(53.4%) in patients with bronchiectasis compared to 63(17.8%) in controls (p<0.001). The occurrence of false positives was higher in subjects with bronchiectasis (26%vs17%;p = 0.003). During follow-up, new nodules were more common among subjects with bronchiectasis (17%vs.12%; p = 0.008). The total number of false positives during follow-up was 29(17.06%) for patients with bronchiectasis vs. 88(12.17%) for controls (p = 0.008).The incidence rate of lung cancer during follow-up was 6.8/1000 and 5.1/1000 person-years for each group respectively (p = 0.62). CONCLUSIONS: Bronchiectasis are common among current and former smokers undergoing lung cancer screening with LDCT. The presence of bronchiectasis is associated with greater incidence of new nodules and false positives on baseline and follow-up screening rounds. This leads to an increase need of diagnostic tests, although the lung cancer occurrence is not different.

Emphysema phenotypes and lung cancer risk.

BACKGROUND: To assess the relationship between lung cancer and emphysema subtypes. OBJECTIVE: Airflow obstruction and emphysema predispose to lung cancer. Little is known, however, about the lung cancer risk associated with different emphysema phenotypes. We assessed the risk of lung cancer based on the presence, type and severity of emphysema, using visual assessment. METHODS: Seventy-two consecutive lung cancer cases were selected from a prospective cohort of 3,477 participants enrolled in the Clínica Universidad de Navarra's lung cancer screening program. Each case was matched to three control subjects using age, sex, smoking history and body mass index as key variables. Visual assessment of emphysema and spirometry were performed. Logistic regression and interaction model analysis were used in order to investigate associations between lung cancer and emphysema subtypes. RESULTS: Airflow obstruction and visual emphysema were significantly associated with lung cancer (OR = 2.8, 95%CI: 1.6 to 5.2; OR = 5.9, 95%CI: 2.9 to 12.2; respectively). Emphysema severity and centrilobular subtype were associated with greater risk when adjusted for confounders (OR = 12.6, 95%CI: 1.6 to 99.9; OR = 34.3, 95%CI: 25.5 to 99.3, respectively). The risk of lung cancer decreases with the added presence of paraseptal emphysema (OR = 4.0, 95%CI: 3.6 to 34.9), losing this increased risk of lung cancer when it occurs alone (OR = 0.7, 95%CI: 0.5 to 2.6). CONCLUSIONS: Visual scoring of emphysema predicts lung cancer risk. The centrilobular phenotype is associated with the greatest risk.

Adenosine triphosphate (ATP) and adenosine cause similar vasodilator effect in patients undergoing stress perfusion cardiac magnetic resonance imaging.

To evaluate the vasodilator effect of adenosine triphosphate (ATP) compared with adenosine in stress perfusion cardiac magnetic resonance (CMR) examinations. A total of thirty-three patients underwent clinically indicated stress/rest perfusion CMR examination following intravenous injection of a total dose of 0.2 mmol/kg of gadobutrol. Individuals were randomly assigned to ATP (160 mcg/kg/min) or adenosine (140 mcg/kg/min). The vasodilator effect of both drugs was analyzed by comparing differences in heart rate, symptoms during stress, and semiquantitative myocardial and splenic perfusion parameters, including time, time to peak, upslope, myocardial perfusion reserve index, tissue perfusion values, splenic and myocardial signal intensity ratios, and splenic-to-myocardial signal intensity ratios. No significant difference was found in heart rate variation between the stressors (26.1 ± 19.1 bpm for ATP vs. 21.7 ± 17.3 bpm for adenosine, p = 0.52). Patients receiving ATP referred less pronounced clinical symptoms. Semiquantitative myocardial perfusion parameters were comparable, and patients in the adenosine and ATP groups showed similar myocardial perfusion reserve index values (2.34 [1.62-2.73] vs 1.63 [1.29-2.10], p = 0.07). Splenic switch off was visually confirmed in all patients and estimated spleen to myocardium ratio was similar (0.92 [0.53-1.09] vs 0.81 [0.53-0.86] with ATP and adenosine, respectively, p = 0.12). Both ATP and adenosine are potent coronary vasodilators that can be safely employed in stress-CMR. Both stressor cause similar hyperemic response. Splenic switch-off can be used to assess stress adequacy in patients undergoing stress-CMR with either adenosine or ATP.

Clinical features and short-term outcomes of cancer patients with suspected and unsuspected pulmonary embolism: the EPIPHANY study.

The study aimed to identify predictors of overall 30-day mortality in cancer patients with pulmonary embolism including suspected pulmonary embolism (SPE) and unsuspected pulmonary embolism (UPE) events. Secondary outcomes included 30- and 90-day major bleeding and venous thromboembolism (VTE) recurrence.The study cohort included 1033 consecutive patients with pulmonary embolism from the multicentre observational ambispective EPIPHANY study (March 2006-October 2014). A subgroup of 497 patients prospectively assessed for the study were subclassified into three work-up scenarios (SPE, truly asymptomatic UPE and UPE with symptoms) to assess outcomes.The overall 30-day mortality rate was 14%. The following variables were associated with the overall 30-day mortality on multivariate analysis: VTE history, upper gastrointestinal cancers, metastatic disease, cancer progression, performance status, arterial hypotension <100 mmHg, heart rate >110 beats·min-1, basal oxygen saturation <90% and SPE (versus overall UPE).The overall 30-day mortality was significantly lower in patients with truly asymptomatic UPE events (3%) compared with those with UPE-S (20%) and SPE (21%) (p<0.0001). Thirty- and 90-day VTE recurrence and major bleeding rates were similar in all the groups.In conclusion, variables associated with the severity of cancer and pulmonary embolism were associated with short-term mortality. Our findings may help to develop pulmonary embolism risk-assessment models in this setting.

Prognostic value of computed tomography pulmonary angiography indices in patients with cancer-related pulmonary embolism: Data from a multicenter cohort study.

OBJECTIVE: To analyze the prognostic value of pulmonary artery obstruction versus right-ventricle (RV) dysfunction radiologic indices in cancer-related pulmonary embolism (PE). METHODS: We enrolled 303 consecutive patients with paraneoplastic PE, evaluated by computed tomography pulmonary angiography (CTPA) between 2013 and 2014. The primary outcome measure was serious complications at 15days. Multivariate analyses were conducted by using binary logistic and robust regressions. Radiological features such as the Qanadli index (QI) and RV dysfunction signs were analyzed with Spearman's partial rank correlations. RESULTS: RV diameter was the only radiological variable associated with an adverse outcome. Subjects with enlarged RV (diameter>45mm) had more 15-day complications (58% versus 40%, p=0.001). The QI correlated with the RV diameter (r=0.28, p<0.001), left ventricle diameter (r=-0.19, p<0.001), right ventricular-to-left ventricular diameter ratio (r=0.39, p<0.001), pulmonary artery diameter (r=0.22, p<0.001), and pulmonary artery/ascending aorta ratio (r=0.27, p<0.001). A QI≥50% was only associated with 15-day complications in subjects with enlarged RV, inverted intraventricular septum, or chronic cardiopulmonary diseases. The central or peripheral PE location did not affect the correlations among radiological variables and was not associated with clinical outcomes. CONCLUSIONS: Right ventricular dysfunction signs in CTPA are more useful than QI in predicting cancer-related PE outcome.

Effect of contrast dose in the quantification of myocardial extra-cellular volume in adenosine stress/rest perfusion cardiac magnetic resonance examinations.

Background Diffuse myocardial fibrosis can be quantified by calculating extra-cellular volume (ECV) from native and post-contrast T1 values using dedicated single bolus contrast medium injection protocols. Purpose To evaluate differences in T1 maps and myocardial ECV measurements in routine stress/rest perfusion cardiovascular magnetic resonance (CMR) examinations after injection of single and double dose of contrast medium. Material and Methods Thirty-seven consecutive patients (30 men; mean age, 62 ± 13 years) underwent clinically indicated adenosine stress/rest perfusion CMR examination to rule out myocardial ischemia following a conventional split-dose contrast medium injection strategy. Native and post-contrast T1 mapping was performed 15 min after the first (0.1 mmol/kg) and second (0.1 mmol/kg) dose of contrast medium using a breath-held Modified Look-Locker Inversion recovery (MOLLI) sequence. Student's t-test for paired samples, Bland-Altman plots, and concordance-correlation coefficients (CCC) for agreement between T1 and ECV calculations after single and double dose of contrast medium were calculated. Intra- and inter-observer agreement for measurements was also analyzed. Results Myocardial T1 values after single and double dose of contrast medium significantly differed (mean difference of 114.1 ± 19.9 ms, P < 0.01). A single dose of contrast agent provided slightly higher ECV values (mean difference of 2.3 ± 1.1%). CCC for ECV calculations was 0.66. Intra- and inter-observer agreement for all measurements was excellent (CCC ≥ 0.83). Conclusion Quantification of myocardial ECV on conventional stress/rest perfusion CMR examination is feasible. T1 maps obtained 15 min after 0.1 mmol/kg of contrast medium provide slightly higher myocardial T1 measurements and ECV values compared with T1 maps obtained after a total dose of 0.2 mmol/kg.

Lung cancer screening: fourteen year experience of the Pamplona early detection program (P-IELCAP).

INTRODUCTION AND OBJECTIVES: European experience regarding lung cancer screening using low-dose chest CT (LDCT) is available. However, there is limited data on the Spanish experience in this matter. Our aim is to present the results from the longest ongoing screening program in Spain. METHODOLOGY: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) is actively screening participants for lung cancer using LDCT since year 2000 following the IELCAP protocol, including spirometric assessments. Men and women, ≥40 years of age, current or former smokers with a tobacco history of ≥10 pack-years are included. Results are compared to those from other European trials. RESULTS: A total of 2989 participants were screened until March 2014 (73% male). A median of 2 (IQR 1-3) annual screening rounds were performed. Sixty lung cancers were detected in 53 participants (73% in StageI). Adenocarcinoma was the most frequent. The lung cancer prevalence and incidence proportion was 1.0% and 1.4%, respectively, with an annual detection rate of 0.41. The estimated 10-year survival rate among individuals with lung cancer was 70%. Chronic obstructive pulmonary disease and emphysema are important lung cancer predictors. CONCLUSIONS: The experience in Spain's longest lung cancer screening program is comparable to what has been described in the rest of Europe, and confirms the feasibility and efficacy of lung cancer screening using LDCT.

Improving selection criteria for lung cancer screening. The potential role of emphysema.

RATIONALE: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity. OBJECTIVES: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion. METHODS: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema. MEASUREMENTS AND MAIN RESULTS: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%. CONCLUSIONS: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.

Lung cancer screening with low-radiation dose computed tomography after liver transplantation.

Background The prognosis of non-cutaneous malignancies after liver transplantation is dismal, mainly because most cases are diagnosed at advanced stages. In the last decade, studies have shown the potential role of screening for lung cancer with low-radiation dose computed tomography. Material and Methods Fifty-nine liver transplant recipients with a cumulative dose of smoking greater than 10 pack-years were enrolled in a lung cancer screening program using yearly low-radiation dose computed tomography. Results Lung cancer was diagnosed in 7 patients (11.8%), 5 of which were in stage Ia at diagnosis. Patients with lung cancer were significantly older (median age 66 vs. 58 years), had a higher cumulative history of smoking, and had emphysema more frequently than patients without cancer. Conclusions Screening for lung cancer with low-radiation dose computed tomography in liver transplant recipients results in the diagnosis of lung cancer in early stages.

Smokers with CT detected emphysema and no airway obstruction have decreased plasma levels of EGF, IL-15, IL-8 and IL-1ra.

RATIONALE: Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown. OBJECTIVE: TO COMPARE THE PLASMA CYTOKINE PROFILES IN TWO GROUPS OF CURRENT OR FORMER SMOKERS WITHOUT AIRWAY OBSTRUCTION: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema. METHODS: Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1ß, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors. RESULTS: 160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (-0.317, p = 0.01), IL-15 (-0.21, p = 0.01), IL-8 (-0.180, p = 0.02) and IL-1ra (-0.220, p = 0.03) in subjects with emphysema and normal spirometry. CONCLUSIONS: Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.

Allograft morphology and function in heart transplant recipients surviving more than 15 years by magnetic resonance imaging and dual-source computed tomography.

OBJECTIVE: Cardiac allograft vasculopathy and late graft failure are the main limiting factors of long-term success of heart transplantation, and little is known about graft function in the long-term survivors. The aim of this study was to assess the ventricular function and the allograft vasculopathy in long-term survivors (>15 years) with the cardiac magnetic resonance imaging (MRI) and dual-source computed tomography (DSCT) coronary angiogram. METHODS: In our database, 34 cardiac recipients have more than 15 years of follow-up and were evaluated for this study; 22 (65%) of them were enrolled. Mean age at transplant was 46 ± 13.5 years, mean donor age was 28.5 ± 10.1 years, and mean graft ischemic time was 189 ± 58 min. Mean follow-up was 18.5 ± 2.4 years (range 15-22). All patients underwent cardiac MRI and DSCT. RESULTS: Mean left ventricular (LV) volumes indexed to the body surface area (BSA) were within normal range: the end-diastolic volume/BSA was 61 ± 16 ml m(-2), end-systolic volume/BSA was 22 ± 15 ml m(-2), stroke volume/BSA was 38 ± 6 ml m(-2), LV mass/BSA: 72 ± 18 g m(-2), and mean ejection fraction (EF) was 0.59 ± 0.08. Two patients (9%) showed a global cardiac hypokinesia and two other patients (9%) showed akinesia of one segment. At DSCT, 41% of patients had a strictly normal coronary angiogram, 41% had wall thickening and 18% presented a least one >60% stenosis. CONCLUSIONS: Cardiac MRI and DSCT coronary angiogram revealed a normal graft function and morphology after more than 15 years of transplantation. However, a certain number of patients have significant cardiac allograft vasculopathy and another consistent group has initial disease. These patients deserve further follow-up and tailoring of the immunosuppressive regimen.

Low-dose volumetric computed tomography for quantification of emphysema in asymptomatic smokers participating in an early lung cancer detection trial.

PURPOSE: High-resolution computed tomography (CT) is a validated method to quantify the extent of pulmonary emphysema. In this study, we assessed the reliability of low-dose volumetric CT (LDCT) for the quantification of emphysema and its correlation with spirometric indices of airway obstruction. MATERIALS AND METHODS: The study population consisted of 102 consecutive current and former smokers participating in a lung cancer screening trial. All subjects underwent spirometry testing and LDCT at entry and a LDCT after 12 months. The extent of emphysema was estimated by 2 techniques; by using the lung attenuation threshold analysis and by visual assessment of the 2 independent radiologists. The reproducibility of these determinations was assessed using test-retest reliability and kappa coefficient of agreement. The correlation of LDCT-based emphysema determinations with indices of airway obstruction on spirometry was also calculated. RESULTS: Eighty percent of the participants were male, with a mean (standard deviation) age of 54.5 (7.5) years, and median pack-years (interquartile range) of 20 (24). Test-retest reliability of all LDCT-based emphysema determinations was very good (intraclass correlation coefficient of 0.92 for the volume of emphysema, and 0.93 for the emphysema index or emphysema volume/total lung volume). Similarly, there was an excellent interrater agreement for visual assessment of emphysema (kappa coefficient=0.91). Higher volumes of emphysema measured quantitatively or visually significantly correlated with spirometric markers of airway obstruction. CONCLUSIONS: Volumetric LDCT is a reliable and valid technique for the quantification of emphysema in asymptomatic smokers.

Morphological and functional evaluation of intrapericardial cyst as a cause of severe right heart failure: dual source computed tomography and magnetic resonance imaging.

A case of an intrapericardial cyst causing heart failure due to right ventricular compression is presented. Characterization of the lesion and its repercussion on right ventricular function by means of state-of-the-art dual source computed tomography (DSCT) and magnetic resonance imaging (MRI) is shown. The diagnosis of intrapericardial cyst was confirmed after surgical excision and biopsy. Usefulness of these noninvasive techniques for the diagnosis of this rare entity is emphasized.

Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest.

RATIONALE: Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions, early detection, or chemoprevention. OBJECTIVE: To evaluate whether the presence of emphysema on low-radiation-dose CT (LDCT) of the chest is an independent risk factor for lung cancer. METHODS: The study used data from a prospective cohort of 1,166 former and current smokers participating in a lung cancer screening study. All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies. The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated. Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age, gender, smoking history, and the presence of airway obstruction on spirometry. RESULTS: On univariate analysis, the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years, respectively (risk ratio [RR], 3.33; 95% confidence interval [CI], 1.41 to 7.85). Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry (RR, 4.33; 95% CI, 1.04 to 18.16). Multivariate analysis showed that the presence of emphysema (RR, 2.51; 95% CI, 1.01 to 6.23) on LDCT but not airway obstruction (RR, 2.10; 95% CI, 0.79 to 5.58) was associated with increased risk of lung cancer after adjusting for potential cofounders. CONCLUSIONS: Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer.

Early lung cancer detection using spiral computed tomography and positron emission tomography.

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions.

Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors.

PURPOSE: To evaluate the feasibility and safety of intratumoral injection of an adenoviral vector encoding human interleukin-12 genes (Ad.IL-12) and secondarily, its biologic effect for the treatment of advanced digestive tumors. PATIENTS AND METHODS: Ad.IL-12 was administered in doses ranging from 2.5 x 10(10) to 3 x 10(12) viral particles, to seven cohorts of patients with advanced pancreatic, colorectal, or primary liver malignancies. Patients were thoroughly assessed for toxicity, and antitumor response was evaluated by imaging techniques, tumor biopsy, and hypersensitivity skin tests. Patients with stable disease and no serious adverse reactions were allowed to receive up to 3 monthly doses of Ad.IL-12. RESULTS: Twenty-one patients (nine with primary liver, five with colorectal, and seven with pancreatic cancers) received a total of 44 injections. Ad.IL-12 was well tolerated, and dose-limiting toxicity was not reached. Frequent but transient adverse reactions, including fever, malaise, sweating, and lymphopenia, seemed to be related to vector injection rather than to transgene expression. No cumulative toxicity was observed. In four of 10 assessable patients, a significant increase in tumor infiltration by effector immune cells was apparent. A partial objective remission of the injected tumor mass was observed in a patient with hepatocellular carcinoma. Stable disease was observed in 29% of patients, mainly those with primary liver cancer. CONCLUSION: Intratumoral injection of up to 3 x 10(12) viral particles of Ad.IL-12 to patients with advanced digestive malignancies is a feasible and well-tolerated procedure that exerts only mild antitumor effects.

[Screening for lung cancer with low-dose spiral CT: results in 150 asymptomatic subjects]. / Detección precoz del cáncer de pulmón por tomografía computarizada de baja dosis de radiación: resultados de una muestra de 150 individuos asintomáticos.

BACKGROUND AND OBJECTIVE: Our aim is to present initial baseline data from a screening trial on low-dose spiral computed tomography (CT). We describe enrollment criteria and a diagnostic algorithm based on initial low-dose CT findings. SUBJECTS AND METHOD: From September 2000 to May 2001, 150 asymptomatic smokers (age range 40-78 years; mean 55 years) were studied using non-enhanced low-dose spiral CT of the chest. Repeated short-term high resolution CT follow-up was performed for non-calcified pulmonary nodules smaller than 10 mm in diameter. Non-calcified pulmonary nodules 10 mm or larger were considered as potentially malignant and a complementary positron emission tomography (PET) exam was recommended. RESULTS: 54 non-calcified pulmonary nodules were found in 34 out of 141 (24.15%) symptom-free subjects. The diameter was 5 mm or shorter in 24 participants (70.6%), 6-10 mm in 7 (20.6%) and longer than 10 mm in 3 (8.8%) individuals. One patient with a non-calcified pulmonary nodule of at least 10 mm underwent a complementary PET exam, which was positive. Biopsy of this nodule demonstrated lung cancer (squamous cell carcinoma). CT follow-up over one year was decided in the other two subjects having non-calcified pulmonary nodules longer than 10 mm, as no radiographic signs indicative of malignancy were observed in the baseline scan. CONCLUSION: Following this low-dose CT based screening programme, detection of early-stage lung cancer in asymptomatic subjects at high risk of developing the disease is feasible. Further studies are however necessary to pursue more definitive results.

Radiologic screening for lung cancer.

Lung cancer is the leading cause of cancer death. A number of screening trials have been carried out over the past two decades and have failed to demonstrate a reduction of lung cancer-related mortality. Recent advances in new forms of technology--spiral low-dose CT--have resuscitated interest in screening programs. Preliminary results are promising but the outstanding question is whether the magnitude of improvement is sufficient to affect a measurable reduction in lung cancer mortality?