Quantification of growth patterns of screen-detected lung cancers:The NELSON study

Objectives: Although exponential growth is assumed for lung cancer, this has never been quantified in vivo. Aim of this study was to evaluate and quantify growth patterns of lung cancers detected in the Dutch-Belgian low-dose computed tomography (CT) lung cancer screening trial (NELSON), in order to elucidate the development and progression of early lung cancer.Materials and methods: Solid lung nodules found at &gt;= 3 CT examinations before lung cancer diagnosis were included. Lung cancer volume (V) growth curves were fitted with a single exponential, expressed as V = V-1 exp(t/tau), with t time from baseline (days), V-1 estimated baseline volume (mm(3)), and tau estimated time constant. The R-2 coefficient of determination was used to evaluate goodness of fit. Overall volume-doubling time for the individual lung cancer is given by tau*log(2).Results: Forty-seven lung cancers in 46 participants were included. Forty participants were male (87.0%); mean age was 61.7 years (standard deviation, 6.2 years). Median nodule size at baseline was 99.5 mm(3) (IQR: 46.8-261.8 mm(3)). Nodules were followed for a median of 770 days (inter-quartile range: 383-1102 days) before lung cancer diagnosis. One cancer (2.1%) was diagnosed after six CT examinations, six cancers (12.8%) were diagnosed after five CTs, 14 (29.8%) after four CTs, and 26 cancers (55.3%) after three CTs. Lung cancer growth could be described by an exponential function with excellent goodness of fit (R-2 0.98). Median overall volume-doubling time was 348 days (inter-quartile range: 222-492 days).Conclusion: This study based on CT lung cancer screening provides in vivo evidence that growth of cancerous small-to-intermediate sized lung nodules detected at low-dose CT lung cancer screening can be described by an exponential function such as volume-doubling time. (C) 2017 Elsevier B.V. All rights reserved.</p

Promiscuous Binding of Invariant Chain-Derived CLIP Peptide to Distinct HLA-I Molecules Revealed in Leukemic Cells

Antigen presentation by HLA class I (HLA-I) and HLA class II (HLA-II) complexes is achieved by proteins that are specific for their respective processing pathway. The invariant chain (Ii)-derived peptide CLIP is required for HLA-II-mediated antigen presentation by stabilizing HLA-II molecules before antigen loading through transient and promiscuous binding to different HLA-II peptide grooves. Here, we demonstrate alternative binding of CLIP to surface HLA-I molecules on leukemic cells. In HLA-II-negative AML cells, we found plasma membrane display of the CLIP peptide. Silencing Ii in AML cells resulted in reduced HLA-I cell surface display, which indicated a direct role of CLIP in the HLA-I antigen presentation pathway. In HLA-I-specific peptide eluates from B-LCLs, five Ii-derived peptides were identified, of which two were from the CLIP region. In vitro peptide binding assays strikingly revealed that the eluted CLIP peptide RMATPLLMQALPM efficiently bound to four distinct HLA-I supertypes (-A2, -B7, -A3, -B40). Furthermore, shorter length variants of this CLIP peptide also bound to these four supertypes, although in silico algorithms only predicted binding to HLA-A2 or -B7. Immunization of HLA-A2 transgenic mice with these peptides did not induce CTL responses. Together these data show a remarkable promiscuity of CLIP for binding to a wide variety of HLA-I molecules. The found participation of CLIP in the HLA-I antigen presentation pathway could reflect an aberrant mechanism in leukemic cells, but might also lead to elucidation of novel processing pathways or immune escape mechanisms

Complications following lung surgery in the Dutch-Belgian randomized lung cancer screening trial

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. 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. 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%). 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. Trial registration number: ISR CTN 63545820

Nodule management protocol of the NELSON randomised lung cancer screening trial

In December 2003, the Dutch-Belgian NELSON trial, a Dutch acronym for "Nederlands-Leuvens Longkanker Screenings ONderzoek", has been launched. Primary objective of the NELSON trial is to investigate whether screening for lung cancer by 16-detector multi-slice CT with 16 mm x 0.75 mm collimation and 15 mm table feed per rotation (pitch = 1.5) in year 1, 2 and 4 wilt lead to a decrease in lung cancer mortality in high risk subjects of at least 25% compared to a control group which receives no screening. In this paper, the screening regimen and the classification and management of the screen-detected nodules at baseline and incidence screening is presented. This is the first large lung cancer screening trial in which the nodule management protocol is based on volumetric nodule assessment and the presence or absence of growth. Furthermore, the quality assurance measures and the NELSON management system (NMS) are presented. (C) 2006 Elsevier Ireland Ltd. All rights reserved

Incidence and Characteristics of Sensory Disturbance and Its Effects on Self-care Activities and Ambulatory Function in Hemiplegic Patients

Incidence and characteristics of sensory disturbance and its effects on self-care activities and ambulatory function in hemiplegic patients were investigated. Tactile, pain and position sense disturbance were examined respectively and were compared with each other according to their severity and regions in which sensory disturbance was observed. In additions, their effects on self-care activities and ambulatory function were also analyzed. As a result, sensory disturbance was found in more than 90% of the patients. However, no statistically significant difference were found in severity level associated with regions of upper and lower extremities where sensory function was not intact well. There were also no statistically significant relationships between severity of sensory disturbance and self-care activities as well as ambulatory function. These results indicate sensory disturbance is a quite popular symptom in hemiplegic patients and even though its disturbance takes place, it can be compensated more easily than motor paralysis by such as vision and patient's attention while performing self-care and ambulatory activities

Quantification of growth patterns of screen-detected lung cancers: The NELSON study

Although exponential growth is assumed for lung cancer, this has never been quantified in vivo. Aim of this study was to evaluate and quantify growth patterns of lung cancers detected in the Dutch-Belgian low-dose computed tomography (CT) lung cancer screening trial (NELSON), in order to elucidate the development and progression of early lung cancer.status: publishe

Quantification of growth patterns of screen-detected lung cancers: The NELSON study

Objectives Although exponential growth is assumed for lung cancer, this has never been quantified in vivo. Aim of this study was to evaluate and quantify growth patterns of lung cancers detected in the Du

Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial (NELSON). Methods Europe's largest, sufficiently powered randomised lung cancer screening trial was designed to determine whether low-dose CT screening reduces lung cancer mortality by >= 25% compared with no screening after 10 years of follow-up. The screening arm (n=7915) received screening at baseline, after 1 year, 2 years and 2.5 years. Performance of the NELSON screening strategy in the final fourth round was evaluated. Comparisons were made between lung cancers detected in the first three rounds, in the final round and during the 2.5-year interval. Results In round 4, 46 cancers were screen-detected and there were 28 interval cancers between the third and fourth screenings. Compared with the second round screening (1-year interval), in round 4 a higher proportion of stage IIIb/IV cancers (17.3% vs 6.8%, p=0.02) and higher proportions of squamous-cell, bronchoalveolar and small-cell carcinomas (p=0.001) were detected. Compared with a 2-year interval, the 2.5-year interval showed a higher non-significant stage distribution (stage IIIb/IV 17.3% vs 5.2%, p=0.10). Additionally, more interval cancers manifested in the 2.5-year interval than in the intervals of previous rounds (28 vs 5 and 28 vs 19). Conclusions A 2.5-year interval reduced the effect of screening: the interval cancer rate was higher compared with the 1-year and 2-year intervals, and proportion of advanced disease stage in the final round was higher compared with the previous rounds