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Background: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. Methods: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm3, if it was 50 to 500 mm3 but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. Results: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. Conclusions: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.) N Engl J Med 2009;361:2221-9. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To retrospectively evaluate whether baseline nodule density or changes in density or nodule features could be used to discriminate between benign and malignant solid indeterminate nodules. Materials and methods: Solid indeterminate nodules between 50 and 500mm3 (4.6–9.8mm) were assessed at 3 and 12 months after baseline lung cancer screening (NELSON study). Nodules were classified based on morphology (spherical or non-spherical), shape (round, polygonal or irregular) and margin (smooth, lobulated, spiculated or irregular). The mean CT density of the nodule was automatically generated in Hounsfield units (HU) by the Lungcare© software. Results: From April 2004 to July 2006, 7310 participants underwent baseline screening. In 312 participants 372 solid purely intra-parenchymal nodules were found. Of them, 16 (4%) were malignant. Benign nodules were 82.8mm3 (5.4mm) and malignant nodules 274.5mm3 (8.1mm) (p =0.000). Baseline CT density for benign nodules was 42.7HU and for malignant nodules −2.2HU (p =ns). The median change in density for benign nodules was −0.1HU and for malignant nodules 12.8HU (p <0.05). Compared to benign nodules, malignant nodules were more often non-spherical, irregular, lobulated or spiculated at baseline, 3-month and 1-year follow-up (p <0.0001). In the majority of the benign and malignant nodules there was no change in morphology, shape and margin during 1 year of follow-up (p =ns). Conclusion: Baseline nodule density and changes in nodule features cannot be used to discriminate between benign and malignant solid indeterminate pulmonary nodules, but an increase in density is suggestive for malignancy and requires a shorter follow-up or a biopsy. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. Material and methods: This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Results: Of the 469 nodules, 387 (83%) were between 50 and 500mm3, 82 (17%) >500mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103mm3 (range 50–5486mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32–0.43). Conclusion: In solid non-calcified nodules larger than 50mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power. [Copyright &y& Elsevier]

The newly introduced Response Evaluation Criteria in Solid Tumors (RECIST), which relies on a single largest dimension of tumor rather than on the product of perpendicular diameters World Health Organisation (WHO) is intended to simplify the assessment of tumor response. Purpose: Is to evaluate the performance and validity of the RECIST compared to the WHO criteria. Design: Thirty-four consecutive patients with bidimensionally measurable malignant pleural mesothelioma (MPM) were evaluated prospectively. Results: In 27% (9/34) a discrepancy was found between the WHO and RECIST response evaluation 9% (3/34) concerned best responses and 18% (6/34) objective confirmed responses. In 24% (8/34) disease progression was missed by RECIST. The percentage of patients in whom one or more discordance''s between WHO and RECIST were detected was 47, 88% due to underscoring by RECIST. In a subgroup of 24 MPM patients with bidimensionally measurable pleural lesions only, the discrepancy rate was 29%, always due to underscoring by RECIST. However, when in the same subgroup the modified RECIST response evaluation was used the discrepancy rate was 21% and in all cases due to underscoring by WHO. Conclusion: For MPM bidimensional WHO response evaluation cannot automatically be replaced by RECIST because MPM has a non-spherical growth pattern. Our recommendation is to use the WHO criteria for bidimensional measurable lesions, RECIST for unidimensional measurable lesions and a modified RECIST response evaluation, in which the short axis perpendicular to the chest wall is used, for thickened pleural rind disease, according to the method used in the recently completed pemetrexed (Alimta®) trial for MPM. [Copyright &y& Elsevier]

The purpose of this document is to provide recommendations for the selection of the optimal target population for lung cancer screening trials with Spiral Computer Tomography based on an analysis of risk factors and high-risk populations. Our recommendations are to include current or ex-smokers (<5 years) with a smoking history of at least 30 years and an average consumption of at least 20 cigarettes a day. When these selection criteria are applied there is no need for a lower age cut-off. Elderly people can be included as long as their life expectancy is more than 10 years. Participants should be fit enough to undergo thoracic surgery. They may have a history of previous cancer, provided that the cancer has been curatively treated at least 5 years ago without evidence of relapse, except for breast cancer, melanoma and hypernephroma. People with an inability to lie flat, who are unable to hold their breath for 20 s, with a body weight above 140 kg, a chest CT scan within 1 year before enrolment or a previous pneumonectomy should not be invited. The inadequacy of the unit ‘Pack-Years’ (PY) to estimate the individual lung cancer risk is recognised, and future initiatives to develop an appropriate lung cancer risk model are encouraged. [Copyright &y& Elsevier]

Pulmonary blastoma (PB) is a rare malignant tumor of the lung. Treatment is primarily surgical, although, combination chemotherapy has been reported to result in objective responses in inoperable tumors or after incomplete resections. To our knowledge, this is the first report of a very radiosensitive PB, which showed major tumor reduction after several fractions of radiotherapy without further tumor regression after additional chemotherapy with cisplatin and etoposide. The literature on the treatment of PB is reviewed. [Copyright &y& Elsevier]

Investigates the possible protective effects of N-acetylcysteine (NAC) on prolonged in vivo exposure to different subtoxic but clinically realistic oxygen levels. Lung tissue appearance; Bronchoalveolar lavage; Effect on type II cells; Cytochemical analysis of isolated type II cells.

Investigates the effects of prolonged subtoxic levels of hyperoxia on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF) and isolated rat type II cells. Survival and body weight of rats; Effects of hyperoxia on whole lung tissue; Effects of hyperoxia on fluid composition.

Presents a study on the protective aspects of N-acetylcysteine associated with hyperoxic induction in lung injury, in rat type II lung cells. Methodology and materials employed; Results of the study; Statistical data supporting the results.

Presents a study on the influence of hyperoxia on ...glutamyltransferase activity in rat type II lung cells. Methodology and materials employed; Findings of the study; Statistical information supporting the study.

n analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization-triple quadrupole-tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3) pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: It is believed that making an informed decision about (screening) participation is associated with better health-related quality of life (HRQoL) outcomes. This is the first study in cancer screening to explore this association in subjects participating in a lung cancer computed tomography (CT) screening trial. Methods: Participants that made either an informed decision to participate (n =155) or not (n =133) were selected for this study. Differences in HRQoL, measured as generic HRQoL (Short Form 12 [SF-12] and EuroQol questionnaire [EQ-5D]), anxiety/distress (State-Trait Anxiety Inventory [STAI-6], Impact of Event Scale [IES] and Consequences of Screening-Lung Cancer [COS-LC]), were tested with Mann–Whitney U tests and ANOVA at three assessment points (when deciding about participation, before trial randomisation and 2months after receiving the CT result). Results: Subjects who made an informed decision to participate had no better scores than those who did not make an informed decision for 23 out of 24 HRQoL comparisons, except for a better mean score for mental health (Mental Component Summary (MCS)=53.9±9.2 versus 51.0±10.1, p =0.003) before randomisation. For subjects with an indeterminate CT result (n =64), no significant differences were found between subjects with (n =35) or without (n =29) an informed decision. Conclusion: Subjects who did not make an informed decision to participate in lung cancer CT screening trial did not experience worse HRQoL during screening than subjects who did make an informed decision, either in general or after receiving an indeterminate result. [Copyright &y& Elsevier]

Study objectives: Relapse-free survival in patients with sulcus superior tumors. Design: Prospective registration study. Setting: Department of surgical oncology of a university hospital. Patients: Twenty-one patients treated with preoperative radiotherapy (46 Gy), lobectomy and chest-wall resection, and intraoperative radiotherapy (10 Gy). Results: After a median follow-up of 18 months, I8 patients (85%) were free from locoregional relapse, while 8 patients were still alive. Conclusions: The results show that this protocol can achieve excellent local tumor control and can even be used for palliative treatment. [ABSTRACT FROM AUTHOR]

Late diagnosis of lung cancer is still the main reason for high mortality rates in lung cancer. Lung cancer is a heterogeneous disease which induces an immune response to different tumor antigens. Several methods for searching autoantibodies have been described that are based on known purified antigen panels. The aim of our study is to find evidence that parts of the antigen-binding-domain of antibodies are shared among lung cancer patients. This was investigated by a novel approach based on sequencing antigen-binding-fragments (Fab) of immunoglobulins using proteomic techniques without the need of previously known antigen panels. From serum of 93 participants of the NELSON trial IgG was isolated and subsequently digested into Fab and Fc. Fab was purified from the digested mixture by SDS-PAGE. The Fab containing gel-bands were excised, tryptic digested and measured on a nano-LC-Orbitrap-Mass-spectrometry system. Multivariate analysis of the mass spectrometry data by linear canonical discriminant analysis combined with stepwise logistic regression resulted in a 12-antibody-peptide model which was able to distinguish lung cancer patients from controls in a high risk population with a sensitivity of 84% and specificity of 90%. With our Fab-purification combined Orbitrap-mass-spectrometry approach, we found peptides from the variable-parts of antibodies which are shared among lung cancer patients. [ABSTRACT FROM AUTHOR]

Rationale: Accurate measurement of subsolid pulmonary nodules (SSN) is becoming increasingly important in the management of these nodules. SSNs were previously quantified with time-consuming manual measurements. The aim of the present study is to test the feasibility of semi-automatic SSNs measurements and to compare the results to the manual measurements. Methods: In 33 lung cancer screening participants with 33 SSNs, the nodules were previously quantified by two observers manually. In the present study two observers quantified these nodules by using semi-automated nodule volumetry software. Nodules were quantified for effective diameter, volume and mass. The manual and semi-automatic measurements were compared using Bland-Altman plots and paired T tests. Observer agreement was calculated as an intraclass correlation coefficient. Data are presented as mean (SD). Results: Semi-automated measurements were feasible in all 33 nodules. Nodule diameter, volume and mass were 11.2 (3.3) mm, 935 (691) ml and 379 (311) milligrams for observer 1 and 11.1 (3.7) mm, 986 (797) ml and 399 (344) milligrams for observer 2, respectively. Agreement between observers and within observer 1 for the semi-automatic measurements was good with an intraclass correlation coefficient >0.89. For observer 1 and observer 2, measured diameter was 8.8% and 10.3% larger (p<0.001), measured volume was 24.3% and 26.5% larger (p<0.001) and measured mass was 10.6% and 12.0% larger (p<0.001) with the semi-automatic program compared to the manual measurements. Conclusion: Semi-automated measurement of the diameter, volume and mass of SSNs is feasible with good observer agreement. Semi-automated measurement makes quantification of mass and volume feasible in daily practice. [ABSTRACT FROM AUTHOR]

Introduction: Classification of COPD is currently based on the presence and severity of airways obstruction. However, this may not fully reflect the phenotypic heterogeneity of COPD in the (ex-) smoking community. We hypothesized that factor analysis followed by cluster analysis of functional, clinical, radiological and exhaled breath metabolomic features identifies subphenotypes of COPD in a community-based population of heavy (ex-) smokers. Methods: Adults between 50-75 years with a smoking history of at least 15 pack-years derived from a random population-based survey as part of the NELSON study underwent detailed assessment of pulmonary function, chest CT scanning, questionnaires and exhaled breath molecular profiling using an electronic nose. Factor and cluster analyses were performed on the subgroup of subjects fulfilling the GOLD criteria for COPD (post-BD FEV1/FVC < 0.70). Results: Three hundred subjects were recruited, of which 157 fulfilled the criteria for COPD and were included in the factor and cluster analysis. Four clusters were identified: cluster 1 ( n = 35; 22%): mild COPD, limited symptoms and good quality of life. Cluster 2 ( n = 48; 31%): low lung function, combined emphysema and chronic bronchitis and a distinct breath molecular profile. Cluster 3 ( n = 60; 38%): emphysema predominant COPD with preserved lung function. Cluster 4 ( n = 14; 9%): highly symptomatic COPD with mildly impaired lung function. In a leave-one-out validation analysis an accuracy of 97.4% was reached. Conclusions: This unbiased taxonomy for mild to moderate COPD reinforces clusters found in previous studies and thereby allows better phenotyping of COPD in the general (ex-) smoking population. [ABSTRACT FROM AUTHOR]

Summary: Background: Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic activity, and we hypothesised that its use in the maintenance setting could improve outcomes. Methods: In this open-label, multicentre, randomised phase 3 study, eligible patients had proven malignant pleural or peritoneal mesothelioma and had received a minimum of four cycles of first-line treatment containing at least pemetrexed, with or without cisplatin or carboplatin, and had not progressed on this treatment. Patients were randomly assigned (in a 1:1 ratio, stratified by previous first-line chemotherapy, histological subtype, and recruiting hospital) to receive thalidomide 200 mg per day (including a 2 week run in of 100 mg per day) plus active supportive care or active supportive care alone until disease progression. Patients were required to be registered and to start treatment with thalidomide within 10 weeks after the end of the first-line chemotherapy. Thalidomide was given for a maximum of 1 year or until unacceptable toxicity. The primary endpoint was time to progression. The primary analyses were by intention to treat. The study is registered, ISRCTN13632914. Findings: Between May 11, 2004, and Dec 23, 2009, we randomly assigned 222 patients, 111 in each group (one patient on active supportive care later withdrew consent and was excluded from analyses). At the time of this final analysis, median follow-up was 33·1 months (IQR 22·3–66·8), and physician-reported disease progression had occurred in 104 patients in the thalidomide group and 107 in the active supportive care group; 92 patients in the thalidomide group and 93 in the active supportive care group had died. Median time to progression in the thalidomide group was 3·6 months (95% CI 3·2–4·1) compared with 3·5 months (2·3–4·8) in the active supportive care group (hazard ratio 0·95, 95% CI 0·73–1·20, p=0·72). 43 (39%) grade 3 or 4 adverse events were reported in the thalidomide group and 31 (28%) in the active supportive care group; neurosensory events were reported by two (2%) patients on thalidomide and none on active supportive care, cardiac events by two (2%) patients on thalidomide and three (3%) on active supportive care, and thromboembolic events by three (3%) patients on thalidomide and none on active supportive care. Interpretation: No benefit was noted in time to progression with the addition of thalidomide maintenance to first-line chemotherapy. Different treatment strategies are needed to improve outcomes in patients with malignant mesothelioma. Funding: Dutch Cancer Society (KWF), Eli Lilly, NSW Dust Disease Compensation Board, University of Sydney, and Cancer Australia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate performance of computer-aided detection (CAD) beyond double reading for pulmonary nodules on low-dose computed tomography (CT) by nodule volume.Methods: A total of 400 low-dose chest CT examinations were randomly selected from the NELSON lung cancer screening trial. CTs were evaluated by two independent readers and processed by CAD. A total of 1,667 findings marked by readers and/or CAD were evaluated by a consensus panel of expert chest radiologists. Performance was evaluated by calculating sensitivity of pulmonary nodule detection and number of false positives, by nodule characteristics and volume.Results: According to the screening protocol, 90.9 % of the findings could be excluded from further evaluation, 49.2 % being small nodules (less than 50 mm(3)). Excluding small nodules reduced false-positive detections by CAD from 3.7 to 1.9 per examination. Of 151 findings that needed further evaluation, 33 (21.9 %) were detected by CAD only, one of them being diagnosed as lung cancer the following year. The sensitivity of nodule detection was 78.1 % for double reading and 96.7 % for CAD. A total of 69.7 % of nodules undetected by readers were attached nodules of which 78.3 % were vessel-attached.Conclusions: CAD is valuable in lung cancer screening to improve sensitivity of pulmonary nodule detection beyond double reading, at a low false-positive rate when excluding small nodules.Key Points: • Computer-aided detection (CAD) has known advantages for computed tomography (CT). • Combined CAD/nodule size cut-off parameters assist CT lung cancer screening. • This combination improves the sensitivity of pulmonary nodule detection by CT. • It increases the positive predictive value for cancer detection. [ABSTRACT FROM AUTHOR]

OBJECTIVES To assess the complication rate in participants of the screen arm of the NELSON lung cancer screening trial who underwent surgical resection and to investigate, based on a literature review, whether the complication rate, length of hospital stay, re-thoracotomy and mortality rates after a surgical procedure were different from those of the non-screening series, taking co-morbidity into account. METHODS Between April 2004 and December 2008, 198 subjects underwent thoracic surgery. Co-morbid conditions were retrieved from the medical records. Postoperative complications were classified as minor and major. RESULTS In total, 182 thoracotomies, 5 thoracotomies after video-assisted thoracoscopic surgery (VATS) and 11 VATS procedures were performed. In these patients, 36% had chronic obstructive lung disease, 16% coronary artery disease, 14% diabetes mellitus and 11% peripheral vascular disease. Following thoracotomy, 47% (88/187) had ≥1 minor (7–57% in literature) and 10% (18/187) ≥1 major complication (2–26% in literature); following VATS, 38% (6/16) had ≥1 minor complication, but no major complications. Seventeen per cent (3/18) of major complications and 21% (20/96) of minor complications were seen in subjects operated for benign disease. The re-thoracotomy rate was 3% and there was no 30-day mortality after thoracotomy or VATS (0–8.3% in literature). The mortality rate of 0% after surgical procedures is low when compared with the non-screening series (0–8.3%); the rate of complications (53%) is within range when compared with the non-screening series (8.5–58%). CONCLUSIONS In conclusion, mortality rates after surgical procedures are lower in the NELSON lung cancer screening trial than those in the non-screening series. The rate of complications is within the same range as in the non-screening series. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the role of conventional bronchoscopy in the diagnostic examination of suspicious screen-detected pulmonary nodules. Findings reveal that 318 suspicious lesions were assessed by bronchoscopy. It indicates that bronchoscopy detected one percent of all cancers identified.

Abstract: Introduction: It is well known that pulmonary tuberculosis is associated with an increased risk of lung cancer. We investigated whether a history of pulmonary tuberculosis is an independent risk factor for lung cancer survival in Caucasian patients. Methods: The data of the prospective population-based cohort of The Rotterdam Study were used. During a mean follow-up time of 18 years, there were 214 incident cases of pathology-proven lung cancer in a source population of 7983 study participants. History of tuberculosis was assessed at baseline by interviewers using standardized questionnaires. Associations of lung cancer survival with the occurrence of pulmonary tuberculosis were assessed using Cox''s proportional hazard regression analysis adjusted for age, gender, pack-years, educational level and tumor stage. Results: A history of tuberculosis was reported in 13 of the 214 subjects with lung cancer. The survival of patients with lung cancer was significantly shorter in subjects with a history of pulmonary tuberculosis (HR=2.36, CI95%: 1.1–4.9), than in subjects without a history of pulmonary tuberculosis with a mean difference of 311 days. Conclusion: The presence of a history of pulmonary tuberculosis may be an important prognostic factor in the survival of lung cancer. [Copyright &y& Elsevier]

Abstract: Background: Lung cancer screening might be a teachable moment for smoking cessation intervention. The objective was to investigate whether a tailored self-help smoking cessation intervention is more effective in inducing smoking cessation compared to a standard brochure in male smokers who participate in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON trial). Methods: Two random samples of male smokers who had received either a standard brochure (n =642) or a tailoring questionnaire for computer-tailored smoking cessation information (n =642) were sent a questionnaire to measure smoking behaviour two years after randomisation. Results: Twenty-three percent of the male smokers in the tailored information group returned a completed tailoring questionnaire and thus received the tailored advice. The prolonged smoking abstinence was slightly, but not statistically significant, lower amongst those randomised in the tailored information group (12.5%) compared with the brochure group (15.6%) (OR=0.77 (95%-CI: 0.56–1.06). The level of education and intention to quit smoking significantly predicted smoking cessation at follow-up (p <0.05). The majority of the respondents did not recall whether and which smoking cessation intervention they had received at randomisation after 2-years of follow-up. Conclusion: The current study showed no advantage of tailored smoking cessation information over standard self-help information amongst male smokers with a long term smoking history who participate in a lung cancer screening trial after two years of follow-up. However, the low percentage participants who actually received the tailored advice limited the ability to find an advantage. [Copyright &y& Elsevier]

Abstract: Purpose: To assess local control, overall survival, and toxicity of four-dimensional, risk-adapted stereotactic body radiotherapy (SBRT) delivered while tracking respiratory motion in patients with primary and metastatic lung cancer located in the central chest. Methods: Fifty-eight central lesions of 56 patients (39 with primary, 17 with metastatic tumors) were treated. Fifteen tumors located near the esophagus were treated with 6 fractions of 8Gy. Other tumors were treated according to the following dose escalation scheme: 5 fractions of 9Gy (n =6), then 5 fractions of 10Gy (n =15), and finally 5 fractions of 12Gy (n =22). Results: Dose constraints for critical structures were generally achieved; in 21 patients the coverage of the PTV was reduced below 95% to protect adjacent organs at risk. At a median follow-up of 23months, the actuarial 2-years local tumor control was 85% for tumors treated with a BED >100Gy compared to 60% for tumors treated with a BED ⩽100Gy. No grade 4 or 5 toxicity was observed. Acute grade 1–2 esophagitis was observed in 11% of patients. Conclusion: SBRT of central lung lesions can be safely delivered, with promising early tumor control in patients many of whom have severe comorbid conditions. [Copyright &y& Elsevier]

The article discusses results of a study that examines the effectiveness of low-dose lung cancer screening computed tomography (CT) scans in identifying participants with chronic obstructive pulmonary disease (COPD). The study's design, setting and subjects are discussed. The lung function test outcome showed 38 percent have COPD. The diagnostic model identified 274 individuals with COPD, a sensitivity of 63 percent, 88 percent specificity, 85 false-positives and 76 percent positive predictive value. The study concludes that a low-dose inspiratory and expiratory CT scans can identify individuals with COPD.

Abstract: Background: EORTC study 08021/ILCP 01/03 evaluated the role of consolidation gefitinib, an oral tyrosine kinase inhibitor (TKI), administered in patients with advanced non-small cell lung cancer (NSCLC), not progressing following standard 1st-line chemotherapy. Methods: Patients with advanced NSCLC, not-progressing after four cycles of platinum-based chemotherapy, were randomised to receive either gefitinib 250mg/d or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival (OS). Secondary end-points were progression-free survival (PFS) and toxicity. The study was powered to detect a 28% increase in OS from a median of 11–14.1months (HR=0.78) and planned to randomise 598 patients to observe 514 deaths. Results: After inclusion of 173 patients, the trial was prematurely closed due to low accrual. Baseline characteristics for gefitinib (n =86) and placebo (n =87) arms were well balanced. After a median follow up of 41months, the difference in median OS in the gefitinib and placebo arms was not statistically significant (10.9 and 9.4months, HR 0.83 [95% confidence interval (95% CI) 0.60–1.15]; p =0.2). The difference in median PFS significantly favoured gefitinib (4.1 and 2.9months, HR=0.61, [95% CI 0.45, 0.83]), p =0.0015). Adverse events reported in more than 10% of patients were rash (47% with gefitinib versus 13% with placebo) and diarrhoea (34% with gefitinib versus13% with placebo). Conclusions: Despite its premature closure, this trial confirms previous evidence that consolidation gefitinib is safe and improves PFS. However, no difference in OS was observed in this study (NCT00091156). [ABSTRACT FROM AUTHOR]

Abstract: Background: EORTC study 08021/ILCP 01/03 evaluated the role of consolidation gefitinib, an oral tyrosine kinase inhibitor (TKI), administered in patients with advanced non-small cell lung cancer (NSCLC), not progressing following standard 1st-line chemotherapy. Methods: Patients with advanced NSCLC, not-progressing after four cycles of platinum-based chemotherapy, were randomised to receive either gefitinib 250mg/d or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival (OS). Secondary end-points were progression-free survival (PFS) and toxicity. The study was powered to detect a 28% increase in OS from a median of 11–14.1months (HR=0.78) and planned to randomise 598 patients to observe 514 deaths. Results: After inclusion of 173 patients, the trial was prematurely closed due to low accrual. Baseline characteristics for gefitinib (n =86) and placebo (n =87) arms were well balanced. After a median follow up of 41months, the difference in median OS in the gefitinib and placebo arms was not statistically significant (10.9 and 9.4months, HR 0.83 [95% confidence interval (95% CI) 0.60–1.15]; p =0.2). The difference in median PFS significantly favoured gefitinib (4.1 and 2.9months, HR=0.61, [95% CI 0.45, 0.83]), p =0.0015). Adverse events reported in more than 10% of patients were rash (47% with gefitinib versus 13% with placebo) and diarrhoea (34% with gefitinib versus13% with placebo). Conclusions: Despite its premature closure, this trial confirms previous evidence that consolidation gefitinib is safe and improves PFS. However, no difference in OS was observed in this study (NCT00091156). [Copyright &y& Elsevier]

Background Emphysema and small airway disease both contribute to chronic obstructive pulmonary disease (COPD), a disease characterised by accelerated decline in lung function. The association between the extent of emphysema in male current and former smokers and lung function decline was investigated. Methods Current and former heavy smokers participating in a lung cancer screening trial were recruited to the study and all underwent CT. Spirometry was performed at baseline and at 3-year follow-up. The 15th percentile (Perc15) was used to assess the severity of emphysema. Results 2085 men of mean age 59.8 years participated in the study. Mean (SD) baseline Perc15 was -934.9 (19.5) HU. A lower Perc15 value correlated with a lower forced expiratory volume in 1 s (FEV1) at baseline (r=0.12, p<0.001). Linear mixed model analysis showed that a lower Perc15 was significantly related to a greater decline in FEV1 after follow-up (p<0.001). Participants without baseline airway obstruction who developed it after follow-up had significantly lower mean (SD) Perc15 values at baseline than those who did not develop obstruction (-934.2 (17.1) HU vs -930.2 (19.7) HU, p<0.001). Conclusion Greater baseline severity of CT-detected emphysema is related to lower baseline lung function and greater rates of lung function decline, even in those without airway obstruction. CT-detected emphysema aids in identifying non-obstructed male smokers who will develop airflow obstruction. [ABSTRACT FROM AUTHOR]

Abstract: Purpose of this study was to determine the rate of contamination, defined as lung cancer screening in the control arm, of the Dutch–Belgian randomized lung cancer screening trial (NELSON) as contamination adversely affects the power of a trial. The NELSON cohort includes 15,822 high-risk current and former smokers, aged 50–75 years, equally randomized to the screen and control arm. Questionnaires were sent to a sample of 1460 male subjects of the control arm, stratified on smoking determinants. The response rate was 73.0%. The participants were asked whether they received a chest X-ray or CT scan in the last 4 years and, if so, when and for what reason it had been performed. Examinations performed after randomization because of “Precaution” or “No examination was offered by NELSON” were regarded as contamination. In the first 24 months after randomization 3.1% (2.3–3.8%) of the respondents received a lung cancer screening examination. Contamination reached a non-significant peak within the first 3 months after randomization, with a lower limit of 2.5 and an upper limit of 3.1 per 1000 person-months. This screening rate did not differ from the background rates in the last 18 months before randomization. No significant differences were observed between current and former smokers. In conclusion, the rate of contamination among male subjects of the control arm of the NELSON trial is low and is not likely to jeopardize the power of the trial. [Copyright &y& Elsevier]

Objective: To assess volumetric measurement variability in pulmonary nodules detected at low-dose chest CT with three reconstruction settings.Methods: The volume of 200 solid pulmonary nodules was measured three times using commercially available semi-automated software of low-dose chest CT data-sets reconstructed with 1 mm section thickness and a soft kernel (A), 2 mm and a soft kernel (B), and 2 mm and a sharp kernel (C), respectively. Repeatability coefficients of the three measurements within each setting were calculated by the Bland and Altman method. A three-level model was applied to test the impact of reconstruction setting on the measured volume.Results: The repeatability coefficients were 8.9, 22.5 and 37.5% for settings A, B and C. Three-level analysis showed that settings A and C yielded a 1.29 times higher estimate of nodule volume compared with setting B (P = 0.03). The significant interaction among setting, nodule location and morphology demonstrated that the effect of the reconstruction setting was different for different types of nodules. Low-dose CT reconstructed with 1 mm section thickness and a soft kernel provided the most repeatable volume measurement.Conclusion: A wide, nodule-type-dependent range of agreement between volume measurements with different reconstruction settings suggests strict consistency is required for serial CT studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coronary artery calcium (CAC) and thoracic aorta calcium (TAC) can be detected simultaneously on low-dose, non-gated computed tomography (CT) scans. CAC has been shown to predict cardiovascular (CVD) and coronary (CHD) events. A comparable association between TAC and CVD events has yet to be established, but TAC could be a more reproducible alternative to CAC in low-dose, non-gated CT. This study compared CAC and TAC as independent predictors of all-cause mortality and cardiovascular events in a population of heavy smokers using low-dose, non-gated CT. Methods: Within the NELSON study, a population-based lung cancer screening trial, the CT screen group consisted of 7557 heavy smokers aged 50–75 years. Using a case–cohort study design, CAC and TAC scores were calculated in a total of 958 asymptomatic subjects who were followed up for all-cause death, and CVD, CHD and non-cardiac events (stroke, aortic aneurysm, peripheral arterial occlusive disease). We used Cox proportional-hazard regression to compute hazard ratios (HRs) with adjustment for traditional cardiovascular risk factors. Results: A close association between the prevalence of TAC and increasing levels of CAC was established (p <0.001). Increasing CAC and TAC risk categories were associated with all-cause mortality (p for trend=0.01 and 0.001, respectively) and CVD events (p for trend <0.001 and 0.03, respectively). Compared with the lowest quartile (reference category), multivariate-adjusted HRs across categories of CAC were higher (all-cause mortality, HR: 9.13 for highest quartile; CVD events, HR: 4.46 for highest quartile) than of TAC scores (HR: 5.45 and HR: 2.25, respectively). However, TAC is associated with non-coronary events (HR: 4.69 for highest quartile, p for trend=0.01) and CAC was not (HR: 3.06 for highest quartile, p for trend=0.40). Conclusions: CAC was found to be a stronger predictor than TAC of all-cause mortality and CVD events in a high-risk population of heavy smokers scored on low-dose, non-gated CT. TAC, however, is stronger associated with non-cardiac events than CAC and could prove to be a preferred marker for these events. [Copyright &y& Elsevier]

Summary: Screening for cancer can cause distress. People who perceive their risk of cancer as high may be more vulnerable to distress. This study evaluated whether participants of a lung cancer Computed Tomography (CT) screening trial with a high affective risk perception of developing lung cancer had a higher level of lung cancer-specific distress during CT screening. Furthermore, we evaluated whether participants perceived their risk of developing lung cancer differently 6 months after screening compared with 1 day before screening. A total of 351 subsequent participants of the NELSON-trial (Dutch-Belgian randomized controlled trial for lung cancer screening in high-risk subjects), who were randomized to the screen arm, were asked to fill in questionnaires 1 day before and 6 months after screening. Lung cancer-specific distress (Impact of Event Scale (IES)), generic health-related quality of life (SF-12) and affective risk perception were assessed. One day before screening, the participants with a high affective risk perception (n =47/321, 14.6%) had significantly higher (i.e., worse) median IES scores than participants with a low affective risk perception (11.5 vs. 2.0, p <0.01). Although median IES scores were significantly lower 6 months after screening than 1 day before screening, participants with a high affective risk perception still showed significantly higher IES scores than participants with a low affective risk perception (6.5 vs. 1.0, p <0.01). Six months after screening, significantly less participants (10.5%) felt that their risk of developing lung cancer was high than 1 day before screening (14.5%) (p <0.01). Levels of distress were not severe, but were elevated compared to participants with a low affective risk perception, and therefore, attention for this group is recommended. [Copyright &y& Elsevier]

Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. Material and Methods: This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Results: Of the 469 nodules, 387 (83%) were between 50 and 500mm3, 82 (17%) >500mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103mm3 (range 50-5486mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43). Conclusion: In solid non-calcified nodules larger than 50mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power. [ABSTRACT FROM AUTHOR]

The article reports on results of a study of the impact of computed tomography (CT) screening for lung cancer on participants in a randomized controlled trial. A description of the experimental set-up and measurement method is provided. The study concludes that potential adverse effects of CT screening for lung cancer on health-related quality of life demonstrated no negative effects.

Summary: The high frequency of non-calcified pulmonary nodules (NCN) <10mm incidentally detected on a multi-detector CT (MDCT) of the chest raises the question of how clinicians and radiologists should deal with these nodules. Management algorithms for solitary pulmonary nodules >10mm do not carry across to sub-centimeter lesions. Purpose of this review is to provide a 10-step approach for routinely detected sub-centimeter NCN on a MDCT in healthy persons in order to be able to make an optimal discrimination between benign and malignant NCNs. Recommendations are primarily based on individual cancer risk, the presence or absence of calcifications and nodule size. In nodules >4–5mm nodule consistency, margin and shape should be taken into account. Next steps in the nodule evaluation are the assessment of localization, nodule number, presence or absence of growth and volume doubling time. Growth is defined as a volume doubling time of 400 days or less, based on volumetry. For nodules <4mm, a follow-up CT at 12 months is recommended in high risk persons, whilst for low-risk persons no follow-up is needed. If no growth is observed at 12 months, no further follow-up is required. For solid, smooth or attached indeterminate NCN between 5 and 10mm we recommend an annual repeat scan, whilst for purely intra-parenchymal nodules a 3-month repeat scan should be made to assess growth. Growing lesions with a volume doubling time <400 days require further work-up and diagnosis, otherwise an annual repeat scan to assess growth is recommended. [Copyright &y& Elsevier]

Summary: Many patients with various forms of cancer develop sooner or later malignant pleural effusions, resulting in feelings of discomfort and reduced quality of life. Several palliative options exist, including repeated thoracocentesis and pleurodesis with a sclerosing agent. However, these “therapeutic” possibilities are not always successful and sometimes even contraindicated. Also, patients need to visit the hospital regularly or have to stay hospitalised for several days. A chronic indwelling pleural catheter could provide a simple, completely outpatient way to provide respiratory relief and improvement in quality of life in patients with malignant pleural effusions. We evaluated retrospectively the course of 17 patients with malignant pleural effusions who were treated with a chronic indwelling pleural catheter (PleurX®). Eligible patients were selected in the years 2001–2003 from a single institution. In 70–80% of patients, catheter use was uncomplicated and provided significant symptom relief. Mean duration of catheter use was 2.3 (range 1–6) months. Mean fluid removal was 360 (range 150–1000cc) per 24h in the first weeks of treatment. Infection was seen in two (12%) patients, dislocation of the catheter in three (18%). In the final analysis, catheter use was unsatisfactory in two patients (12%). We conclude that a chronic indwelling catheter is a very useful tool in the management of recurrent malignant pleural effusions. Treatment can be accomplished completely at home, whereas complications are rare. [Copyright &y& Elsevier]

Purpose: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT).Methods and Materials: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of ≥1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure.Results: Of 43 patients who received doses ≥50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14–22) and the median progression-free survival was 12 months (95% confidence interval 6–18).Conclusion: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity. [Copyright &y& Elsevier]