Kris Nackaerts

Management of Lung Nodules Detected by Volume CT Scanning

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 mm(3), if it was 50 to 500 mm(3) 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.)

Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.

PURPOSE To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Ground-measured spectral signatures as indicators of ground cover and leaf area index: the case of paddy rice

A methodology is described to use spectral signatures as indicators of the vegetative status in rice paddy cultures. Ground cover and leaf area index (LAI), considered as indicators of above-ground biomass, and were measured in the field using indirect techniques of digitized close-range vertical photography and Licor 2000 instrument readings, as well as direct destructive sampling. Simultaneously, field reflectance values were collected over specific spectral bandwidths using a handheld radiometer. Several vegetation indices were derived from these spectral measurements and their predictive power (individually or in combination) with respect to field-measured ground cover and LAI quantified. The additional effects of plant chlorophyll content, paddy depth, water sediment load, and bottom layer color were also investigated. None of these variables added significantly to the predictive power of the models. The models were refined for intra-seasonal variability and a new growth-stage-dependent variable improved the models’ predictive capabilities. The results demonstrated that the monitoring of paddy rice crop status by means of its spectral signatures appears very promising. # 2001 Elsevier Science B.V. All rights reserved.

Comparative performance of a modified change vector analysis in forest change detection

Sustainable forest management requires accurate and up‐to‐date information, which can nowadays be obtained using digital earth observation technology. This paper introduces a modified change vector analysis (mCVA) approach and conceptually contrasts it against traditional CVA. The results of a comparative study between this change detection algorithm and three other widely used change detection algorithms: standardized differencing, ratioing and selective principal component analysis are summarized. Landsat Thematic Mappper (TM) imagery and detailed change maps of a forested area in Northern Minnesota were used. Change indicators (vegetation indices) were grouped into three conceptually independent categories corresponding to soil, vegetation and moisture characteristics. Change periods of two, four and six years were considered. All change detection outputs were multidimensional and of a continuous nature, and could therefore be subjected to a supervised maximum likelihood algorithm using identical data training sets. Change extraction accuracies were determined by computing overall accuracy and Kappa coefficients of agreement against independent reference datasets. The mCVA outperformed the three other change detection methods in all cases, and we have shown that there is a clear advantage in running mCVA with three change indicator inputs where each input comes from a different change indicator category. Further validations with more detailed reference data are needed to improve this method and test its performance for other types of change events.

Sampling methodology for LAI measurements with LAI-2000 in small forest stands.

Leaf Area Index (LAI) plays a prominent role as an indicator of forest ecosystem condition in research on change detection. For this, rapid and reliable estimation of the effective LAI (LAIe) — this is the ratio of the total one-sided area of vegetation elements over the unit ground area) — at various scales is of utmost importance. We used the Licor LAI-2000 Plant Canopy Analyzer (PCA) for the acquisition of point LAI values within small (about 1 ha) stands. Canopy influences, external to the stand for which LAI was being assessed, and direct sunlight were excluded from respectively the LAIe computations and the fields of view of the PCA sensors by the use of a 270 viewcap. The effect of sampling scheme and data aggregation method on LAIe was quantified by means of a Monte Carlo simulation. The methodology presented is generalized and can be applied to forest stands with different canopy architectures. Our results show that for our study area the LAIe populations are normally distributed. A power function relationship was shown to exist between the relative accuracy of the acquired LAIe value and the sampling intensity. Based on this information, an appropriate sampling scheme can be selected for a predetermined relative accuracy. The method allowed us to quantitatively assess LAIe in small stands often occurring in very heterogeneous environments, which is typically the case for large parts of Western Europe. ©2000 Published by Elsevier Science B.V. All rights reserved.

Man and environment in the territory of Sagalassos, a classical city in SW Turkey

Abstract Since 1990 archaeological research by the Catholic University of Leuven (Belgium) has been carried out at the ancient site of Sagalassos (Aǧlasun, Burdur province, Southwestern Turkey). At first, research focused on the excavation of the city and the study of the immediate vicinity which provided it with raw materials. The main objective was to obtain a clear picture of the history and development of the city. Since 1993 research has also incorporated a study of the territory of the Roman city, from prehistoric to modern times, in order to understand why the site was selected for settlement, why it developed into a middle-sized town, its economy and subsistence, how it affected and exploited the environment, its decline, and what changes have taken place in the district subsequently. The focus has now shifted towards obtaining a better understanding of the linkages between human and environment systems so that inter-relations between the two can be more readily understood. As a result, a number of environmental topics concerning the territory of the Roman city are presently being studied. This territory extended from Lake Burdur in the West to the Aksu canyon in the East, from the Aǧlasun Daǧlari in the North to Mt. Kestel in the South. Interdisciplinary research revealed that for the early Neolithic and the Roman period there was a slightly warmer climate, a richer vegetation and more fertile soils for agricultural practice.

Fatal pulmonary veno-occlusive disease possibly related to gemcitabine

In November 1995, a 57-year-old male was admitted for worsening dyspnea, a dry cough and chest tightness. His medical history was unremarkable, and without cardiopulmonary disease. A central cT4N0M0 adenocarcinoma of the left lung with malignant pericardial effusion was diagnosed. Baseline CEA was 168 mg/l. The patient underwent a thoracoscopic pericardial fenestration with good symptom relief. Pulmonary function tests (PFTs) after this procedure showed a slight restrictive pattern, probably due to left diaphragm palsy: FEV1 83%, VC 89%, TLC 83%, DLCO 82%, and arterial oxygen partial pressure (PO2) 82 mmHg. After informed consent, he was then included in a phase II chemotherapy trial with alternating administration of docetaxel 100 mg/m, and cisplatin 120 mg/m, repeated every 3 weeks up to nine cycles (five docetaxel and four cisplatin) [2]. There was a nearly complete radiological response, CEA fell to 8.2 mg/l. In February 1997, disease progression occurred (CEA 168 mg/l), and treatment with alternating docetaxel 100 mg/m and cisplatin 100 mg/m was restarted (six cycles * Corresponding author. Tel.: +32-16-346802; fax: +3216-346803. E-mail address: johan.vansteenkiste@uz.kuleuven.ac.be (J.F. Vansteenkiste).

Accuracy assessment of probabilistic visibilities

Visual impact studies often make use of Boolean viewshed maps created by standard functions implemented in most raster GIS software. The DEM is used in a deterministic way and possible inaccuracies in the DEM are neglected. Monte Carlo simulations of the errors in the digital elevation data (DEM error) can be used to test the effect of the DEM error on the calculated viewshed. Both an explorational and a quantitative method based on binomial statistics are proposed to analyse the impact of the number of simulations on the accuracy of the probabilistic visibility of a cell. The probabilistic information is used for the creation of a Boolean viewshed map with a known users and/or producers accuracy. The importance of this methodology is illustrated.

Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: results from 2 phase I studies.

BACKGROUND The objectives were to determine the maximum tolerated dose (MTD) of pemetrexed and cisplatin with concurrent radiotherapy. Secondary objectives include incidence and nature of acute and late toxicities, tumor response and overall survival. PATIENTS AND METHODS Treatment naïve patients received 1 cycle of cisplatin 80 mg/m(2) in study I (stage III NSCLC), 75 mg/m(2) in study II (LD-SCLC) and pemetrexed 500 mg/m(2) before the phase I part. In study I, patients were treated in cohorts with escalating cisplatin doses (60-80 mg/m(2)), pemetrexed doses (400-500 mg/m(2)) and concurrent escalating radiotherapy doses (66 Gy in 33-27 fractions). In study II, patients were treated with cisplatin 75 mg/m(2) and escalating pemetrexed doses (400-500 mg/m(2)) with concurrent escalating radiotherapy doses (50-62 Gy). RESULTS The trials closed prematurely: study I because of poor accrual, study II because of sponsor decision. Thirteen patients were treated: 4 with NSCLC, 9 with LD-SCLC. No dose-limiting toxicity was observed. There was no grade 4 toxicity, grade 3 hematological toxicity was mild. One patient developed grade 3 acute esophagitis, but was able to complete radiotherapy without delay. Two patients experienced grade 2 late pulmonary toxicity, 1 complete response, 6 partial responses and 1 progressive disease were observed. CONCLUSIONS Although the studies stopped too early to assess MTD, we have demonstrated that the combination of cisplatin and pemetrexed with concurrent radiotherapy up to 66 Gy (33 x 2 Gy) is well tolerated and this new combination shows activity in NSCLC. Pemetrexed is the first 3rd generation cytotoxic found to be tolerable at full dose with concurrent radiotherapy.

Blinded and uniform cause of death verification in a lung cancer CT screening trial

Disease-specific mortality is the final outcome of a lung cancer screening trial, therefore cause of death verification is crucial. The use of death certificates for this purpose is debated because of bias, inaccurate completion and incorrect ante mortem diagnoses. A cause of death evaluation process was designed to ensure a uniform and unbiased determination of the graduation of certainty that lung cancer was the underlying cause of death. An independent clinical expert committee will review the medical files of all deceased participants once diagnosed with lung cancer and will make use of a flow chart and predetermined criteria. A pilot study of fifty cases was conducted to determine the performance of this process and to compare the outcome with the official death certificates. The independent review has shown an agreement of 90% (kappa 0.65), which demonstrates a uniform classification. The sensitivity and specificity of the death certificates for lung cancer specific mortality were 95.2 and 62.5%. This demonstrates a limited distinctive character of the death certification process in lung cancer patients. Our results imply that the final outcome of a lung cancer screening trial cannot reliably be established without predetermined criteria and an independent review of blinded cases.