Virtual Library
Start Your Search
U. Pastorino
Moderator of
-
+
E01 - LDCT Screening (ID 1)
- Event: WCLC 2013
- Type: Educational Session
- Track: Imaging, Staging & Screening
- Presentations: 4
- Moderators:U. Pastorino, J.M.A. Daniels
- Coordinates: 10/28/2013, 14:00 - 15:30, Parkside Auditorium, Level 1
-
+
E01.1 - Risk Stratification for Lung Cancer Screening Studies (ID 372)
14:00 - 15:30 | Author(s): M. Tammemagi
- Abstract
Abstract
-
+
E01.2 - Volumetrics for Nodule Assessment (ID 373)
14:00 - 15:30 | Author(s): M. Oudkerk, M. Heuvelmans
- Abstract
- Presentation
Abstract
Introduction Lung cancer is a major health problem with no improvement in survival over the last decades. At time of diagnosis, lung cancer is often already in advanced stage, with 5-year survival of no more than 15%. Currently, several lung cancer screening trials investigating whether early detection of lung cancer in high-risk individuals will reduce lung cancer mortality are ongoing. In 2011, the National Lung Screening Trial (NLST), was the first and to date only reporting a 20% decrease in lung cancer mortality when three rounds of annual low-dose computed tomography (CT) were compared with three annual rounds of chest X-ray screening. A major challenge, however, is the high rate of positive test results reported by the NLST (24.2%). No less than 96.2% of these comprised false-positive test results, causing unnecessary patient anxiety, radiation exposure and cost. The Dutch-Belgian lung cancer screening trial (Dutch acronym: NELSON study) was launched in September 2003. The NELSON study is an ongoing multicentre randomized controlled multi-detector low-dose CT lung cancer screening trial. The primary object is to investigate whether chest CT screening in year 1, 2, 4 and 6.5 will decrease lung cancer mortality by at least 25% in high-risk (ex-)smokers between 50 and 75 years of age compared to a control group receiving no screening. The NELSON study is the first lung cancer screening trial in which nodule management is based on nodule volume, instead of transverse cross-sectional nodule diameter for new nodules, and nodule growth in terms of volume doubling time (VDT) for existing ones. In this presentation, different aspects of nodule management in the NELSON study will be discussed. Volume detection thresholds Sensitive pulmonary nodule detection is crucial not to miss any lung cancer in a screening setting. The sensitivity of nodule detection was investigated by scanning a Lungman phantom according to the standard NELSON protocol. Nodules of five different volumes (range 14–905mm[3]) were randomly positioned in the phantom. A sensitivity of 100% was found for nodules with a volume equal to or larger than 65mm[3] (5mm), and a sensitivity of 60–80% was found for solid nodules with a volume of 14mm[3] (3mm). Since the lung cancer probability of lung nodules smaller than 50mm[3] or 4mm is neglectable, the sensitivity of nodule detection using the NELSON protocol is sufficient for accurate detection of malignant lung nodules. Measurement reproducibility For accurate decision making in serial CT studies, nodule measurement reproducibility is essential. A sub-study of the NELSON trial showed a difference in repeatability among three reconstruction settings, demonstrating that the use of consistent reconstruction parameters is important. Volume measurements of pulmonary nodules obtained at 1mm section thickness combined with a soft kernel were found to be most repeatable. Another sub-study showed that variability on volume measurements is related to nodule size, morphology and location. Besides image reproducibility, interobserver variability in performing semi-automated volume measurements is of major importance in the classification of lung nodules. Gietema et al. found that interobserver correlation was very high (r=0.99) in small-to-intermediate size (15-500mm[3]) nodules. Volume criteria for nodule stratification For solid nodules, and solid components of part-solid nodules, volume was calculated by 3-dimensional volumetric computer assessment, using LungCare software (version Somaris/5:VA70C-W; Siemens Medical Solutions). The final screen result was based on the nodule with largest volume or fasted growth. In the NELSON study, nodules were classified as negative if volume was <50mm[3] (4.6mm diameter if the nodule would have been perfectly spherical), leading to an invitation for the regular next-round CT, as positive if nodule volume was >500mm[3] (>9.8mm diameter), leading to direct referral to a pulmonologist for further workup, and as indeterminate in case of volume of 50-500mm[3]. Indeterminate nodules underwent a 6-week to 3-month follow-up low-dose CT for growth assessment. Volumetric growth assessment of pulmonary nodules After a nodule has been selected by a radiologist, the LungCare software automatically calculates nodule volume. Information is saved in the NELSON Management System (NMS), which calculates the growth in case of a pre-existing nodule. Growth is defined as a change in volume of ≥25% between two subsequent scans according to the formula: Percentage volume change (%) = (V2-V1)/V1)*100 V2 = volume at last CT, and V1 = volume at previous examination. Determination of the volume-doubling time For solid nodules, or solid components of partial-solid nodules with PVC≥25%, the VDT is semi-automatically calculated by the NMS according to the formula: VDT (days) = (ln(2)*Δt)/(ln(V2/V1)) The VDT is used to distinguish between positive screens (VDT<400days), requiring additional diagnostic procedures, indeterminate screens (VDT 400-600days), requiring an extra follow-up CT 12 months after the regular round CT and negative screens (VDT>600days). Using this two-step approach of volume and growth assessment, 2.6% of NELSON baseline screens were positive, and compared to other screening trials, a higher proportion (34.6% at baseline) were true-positive. The NELSON study reported a baseline screen sensitivity of 94.6% and a negative predictive value of 99.9%. Comparison between volumetric and diameter assessment of pulmonary nodules For determining pulmonary nodule size, the use of volume measurements has been found to be more reliable than diameter measurements. In the previously mentioned phantom study, measurements of the manually measured maximal transverse diameter and semi-automated measurements of diameter and nodule volume were compared with actual properties. In both methods, diameter and volume of the spherical nodules were significantly underestimated. In diameter evaluation, the overall underestimation for solid nodules was about 10% using the manual method, compared with less than 4% using the semi-automated method. In volumetry, the overall underestimation for solid nodules was about 25% (translates into 8% diameter underestimation) using the manual method, compared with less than 8% (translates into 2.5% diameter underestimation) using the semi-automated method. It is important to keep in mind that a small change in diameter already corresponds to a considerably higher change in volume. Thus, in lung cancer screening we suggest nodule measurements by semi-automated volumetry should be used. Differences between volume and diameter based nodule management protocol in terms of early lung cancer detection, morbidity, mortality, radiation exposure and costs remain to be demonstrated.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
E01.3 - Molecular Pathology / Profiling of CT Detected Nodules (ID 374)
14:00 - 15:30 | Author(s): W. Lam
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
E01.4 - Implementing Screening: Recommendations From the IASLC (ID 375)
14:00 - 15:30 | Author(s): J.K. Field
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
E09 - Chemoprevention (ID 9)
- Event: WCLC 2013
- Type: Educational Session
- Track: Prevention & Epidemiology
- Presentations: 4
- Moderators:U. Pastorino, P. Yang
- Coordinates: 10/29/2013, 14:00 - 15:30, Bayside 104, Level 1
-
+
E09.1 - Preclinical Models for Lung Cancer Prevention (ID 413)
14:00 - 15:30 | Author(s): L.M. Montuenga, J. Agorreta, S. Vicent, C. Ortiz-De-Solorzano, A. Muñoz, R. Pio
- Abstract
- Presentation
Abstract
Lung cancer risk models and screening protocols are becoming more precise and, consequently, there is an increasing interest in developing new chemoprevention strategies for lung cancer. A number of compounds, among them several phytochemicals, have been proposed as potential lung cancer chemopreventive agents based on studies using rodent models. New preclinical studies involving novel chemopreventive compounds or more efficacious dosing strategies are required and their success will depend in part on the quality of the experimental models. In our presentation we will give an update of the available and newly emerging rodent models for the preclinical study of potential chemopreventive interventions for lung cancer. In order to fully recapitulate the complexities of human lung cancer, different animal models have been developed. These models can be divided into chemically-induced lung cancer and genetically engineered mouse models (GEMMs). Most chemoprevention studies have been performed on mouse models of lung adenocarcinoma (ADC) induced by a number of chemical carcinogens found in tobacco combustion products. The A/J mouse strain has been utilized primarily for these studies since these mice develop lung tumors rapidly after treatment with certain carcinogens such as anthracene, urethane, nicotine-derived nitrosamine ketone (NNK), other nitrosamines, benzo(a)pyrene (BaP), or vinyl carbamate. There are several well established chemically induced mouse ADC models which have been most frequently used in the assessment of the preventive potential of various types of agents: Genetic differences between ADC and squamous cell carcinoma (SCC) are also paralleled in the development of animal models. Skin painting with nitroso-tris-chloroethylurea (NTCU) is the best established protocol to produce lung SCC in susceptible mice and it has already been used for chemoprevention studies. In our lab, we have studied some phenotypic and genetic traits of the NTCU induced SCC, and we have used this model to analyse SCC-specific drug efficacy. GEMMs of lung cancer, mainly leading to adenomas or ADCs have also been used in chemopreventive preclinical studies. A plethora of GEMMs for lung carcinogenesis are available with single or combined genetic alterations in oncogenes or tumor suppressors. Several mouse models of lung cancer have been developed with mutation of Kras as the initiating oncogenic event. In the Kras[LSLG12D/+ ]knock-in mouse model, expression of oncogenic Kras is achieved by intratracheal inoculation with adenoviruses carrying Cre-recombinase The Kras[LSLG12D/+ ]model represents a highly relevant GEMM as it recapitulates many aspects of human ADC oncogenesis, including the full spectrum of lesions from early atypical adenomatous hyperplasia (AAH) to adenocarcinoma, and expresses human NSCLC gene signatures. Interestingly, combined mutant KRAS expression with additional genetic alterations such as p53, PTEN or LKB1 loss results in advanced stages of lung cancer including metastasis. To date, there is only one GEMM leading to pure squamous histology with many human SCC traits, recently developed in kinase-dead IKKα knock-in mice. Some years ago a mouse model for SCLC was developed by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. A newly developed model of SCLC incorporates p130 knockout and accelerates the formation of SCLC. Finally, mouse models for inflammation-driven lung carcinogenesis are helping to understand the role of smoking induced inflammation in lung cancer. We recently found that silica-induced chronic lung inflammation markedly increases the incidence and multiplicity of mouse lung adenomas and ADCs following N-nitrosodimethylamine (NDMA) treatment. These results are in concordance with other animal models that explore the effects of different inflammatory agents in chemically-induced lung tumor promotion. One of the key practical points regarding the relevance of these animal models in developing new chemoprevention strategies is the extent to which they recapitulate human lung cancer multistep progression at the cellular and molecular levels.. The pathological and molecular likes and dislikes between human lung cancer and the most frequently used animal models will be discussed during the presentation. The quantitative assessment of tumor volume progression in cancers affecting internal organs such the lung is more difficult than the assessment of lesions that are superficial (for example, breast or skin). New imaging technologies such as respiratory-gated micro-CT scans for small animals allow performing longitudinal studies on animal models of lung cancer. Micro-CT has been mainly used to monitor tumor growth and to assess the response or the resistance to therapeutic drugs. The potential of micro-CT imaging in lung cancer chemoprevention studies has been already highlighted. Standardization of protocols, improved resolution, more robust and faster image acquisition and, fully automatic and properly validated quantification algorithms need to be implemented before micro-CT imaging can show its full potential in the assessment of chemoprevention therapies.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
E09.2 - Clinical Chemoprevention Studies: Past, Present and Future (ID 414)
14:00 - 15:30 | Author(s): R. Keith
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
E09.3 - Study Design and Response Assessment in Chemoprevention Trials (ID 415)
14:00 - 15:30 | Author(s): E. Szabo
- Abstract
- Presentation
Abstract
The goal of lung cancer chemoprevention is to prevent the development of invasive cancer, but designing early phase intermediate efficacy clinical trials to demonstrate that a strategy is effective remains a “work in progress”. Phase III prevention trials focus on individuals at high risk for cancer and have a lung cancer endpoint. By contrast, phase II trials depend on intermediate endpoints that are surrogates for cancer incidence, in a fashion analogous to shrinkage in tumor size being a surrogate for survival in phase II cancer treatment trials. Examples of such endpoints include premalignant lesions, proliferative indices, and various biomarkers of risk or malignant potential. To be useful, intermediate endpoints should be integrally involved in the process of carcinogenesis, differentially expressed in at-risk vs. normal epithelium, and modulated by effective interventions with little spontaneous fluctuation in expression. Although no intermediate endpoints have been validated as replacements for cancer incidence thus far, the assessment of a variety of such markers can significantly inform drug development and help make decisions regarding subsequent phase III trials. Lung cancer consists of a heterogeneous set of malignancies that presents with diverse molecular and histologic characteristics. The molecular evolution of tobacco related carcinogenesis is not well understood, but histologic evolution of squamous carcinogenesis, with progression from metaplasia through increasing grades of dysplasia and carcinoma in situ, is well described. This allows for a clinical trial design based on pre- and post-treatment bronchial biopsies to assess the response to chemopreventive interventions. Since the rate of progression of dysplasia to invasive cancer is variable, with higher progression rates associated with higher grades of dysplasia, studies assessing dysplasia as an endpoint need to be randomized such that the “spontaneous” reversion rate in the placebo arm can be used as a comparison to account for the effects of the biopsies and for true biologic reversion. This model has been successfully used to study a variety of interventions, including a recent trial of the prostacyclin analogue iloprost that showed improvement in bronchial histology after 6 months of treatment (Keith R et al., Cancer Prev Res 2011;4:793-802). In contrast, the study of the development of adenocarcinomas has been more difficult due to the inability to access tissues from the peripheral lung. The demonstration that helical CT screening reduces lung cancer mortality opens the opportunity to assess the peripheral lung for adenocarcinoma precursor lesions. Veronesi and colleagues (Veronesi G et al., Cancer Prev Res 2011;4;34-42) examined the effect of an inhaled steroid, budesonide, on CT-detected lung nodules, showing nonsignificant modulation of nonsolid lesions only. As persistent nonsolid (ground glass) lesions are more likely to represent lung cancer precursor lesions such as atypical adenomatous hyperplasia or early cancers than solid nodules, future studies should focus on nonsolid lesions only. Alternative designs for trials include a focus on individual biomarkers, panels of biomarkers, or pathways that are deregulated during carcinogenesis. As an example, Gustafson et al. demonstrated that the PI3K pathway is upregulated early during lung carcinogenesis and that an intervention with the drug myo-inositol that resulted in regression of bronchial dysplasia also inhibited PI3K activation in the bronchial epithelium (Gustafson AM et al., Science Trans Med 2010;2:26ra25). These data suggest that upregulated PI3K signaling could potentially identify smokers at increased risk for lung cancer and that pathway inhibition could serve as an endpoint for assessing treatment effect, a hypothesis that requires further testing. The rapidly increasing understanding of the pathogenesis of lung cancer provides an unprecedented opportunity to intervene in the process. Optimization of clinical trial design is required to translate the basic knowledge into clinical realities.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
E09.4 - New Biomarkers for Chemoprevention Studies (ID 416)
14:00 - 15:30 | Author(s): C. Mascaux
- Abstract
- Presentation
Abstract
Smoking exposes the respiratory mucosa to carcinogens in a “field cancerization” process. Smokers develop bronchial lesions, at the pre-invasive stages, preceding the development of invasive lung cancer. Because of the field of cancerization, these lesions are multiple and occur throughout the bronchial airways, which make complete resection of bronchial premalignant lesions impractical. Chemoprevention aims to prevent the development of lung cancer. The administration of chemopreventive agents may be effective, alone or in association with local treatment, in reducing the risk of developing lung cancer. So far no phase III trial testing chemopreventive agents for lung cancer has shown a consistent and reproducible benefit. Therefore no agent can be recommended currently for the chemoprevention of lung cancer (Szabo et al, Chest, 143 (5), Supplement, 2013, e40S-e60S). Future chemoprevention trials should be conducted based on the knowledge of lung carcinogenesis drivers and pathways (Keith et al, Nature Reviews, 10, 2013, 334-343). This would allow the choice of drugs with a better chance of benefit and the customization of the chemoprevention agents. Personalized approaches based on prediction of response to therapy by biomarkers are integrated in lung cancer treatment, with much higher success rate and reduced useless toxicity. In the context of chemoprevention, no or minimal sides effect must be obtained in the high risk population receiving the drug because of the absence of active disease, the fact that the treatment might have to be taken for many years by a large population at high-risk and consequently, the potential huge impact on public health. Therefore biomarkers could play crucial roles as surrogate intermediate endpoint and as predictors of response to targeted treatment. Lung cancers express lower levels of prostacyclin than normal lung tissues. Prostacyclin prevents lung cancer in a variety of mouse models. A randomized phase II trial comparing oral iloprost (a prostacyclin analogue) to placebo in high-risk subjects demonstrated improvement in bronchial histology but only in former smokers (Keith et al, Cancer Prev Res, 4 (6), 2011, 793-802). This placebo-controlled study offered the opportunity for investigation of other potential intermediate endpoints and predictive biomarkers to incorporate into chemoprevention trials. Matched biopsies (baseline-BL and the same site at follow-up-FU after 6 months of Iloprost or placebo) were obtained in 125 high-risk individuals who completed the trial: 40/35 and 25/25 current/former smokers in the Iloprost and placebo arm, respectively. We analyzed 496 biopsies including 4 matched biopsy pairs per patient: the best and the worst histology at BL and the 2 biopsies from same site at FU. Total RNA was extracted from formalin fixed paraffin embedded sections adjacent to the diagnostic section and 14 selected miRNA previously identified in high-grade bronchial preneoplasia were analyzed by qRT-PCR (Mascaux et al, Eur Respir J, 33, 2009, 352-359). The expression of seven miRNAs was significantly correlated with histology at BL. The expression of miR-34c was inversely correlated with histology at BL (p<0.0001) and with change in histology at FU (p=0.0003), independent of treatment or smoking status. Several miRNAs were also found to be differentially expressed in current smokers as compared with former smokers. In current smokers, miR-375 was up-regulated at BL (p<0.0001) and down-regulated after treatment with iloprost (p=0.0023). No miRNA at baseline reliably predicted a response to iloprost. Thus, miR-34c was inversely correlated with BL histology and with histology changes. Mir-34c changes at FU could be used as a quantitative biomarker to assess histological response in formalin-fixed bronchial biopsies in future lung cancer chemoprevention studies (Mascaux et al, Canc Prev Res, 6 (2), 2013, 100-108). This utility of miR-34c to assess the histological response to chemoprevention needs to be further demonstrated prospectively in other chemoprevention trials. The high-throughput gene expression profiling of bronchial epithelium (Gustafson et al, Sci Transl Med, 2 (26), 2010, 26ra25) and in lung preneoplasia (Mascaux et al, J Thor Oncol, 4 (suppl to 9), 2009, abstract PRS.2, page S282) could allow the discovery of new targets for chemoprevention and the possibility of customized lung cancer chemoprevention, by selecting the agents based on the different molecular profile of the individuals at high risk. Thus future chemoprevention trials should be undertaken based on the biological drivers and pathways of lung carcinogenesis. The chemoprevention trials should include the collection of biological samples to allow testing biomarker for their role as surrogate intermediate endpoint, for the selection of the patients who are at higher risk and for the personalization of the chemoprevention approach, with the purpose of optimizing the benefit and avoiding useless toxicity in high-risk but cancer-free individuals.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
Author of
-
+
MS02 - Stem Cells and Epigenetics in Lung Cancer (ID 19)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Biology
- Presentations: 1
- Moderators:G. Sozzi, J. Minna
- Coordinates: 10/28/2013, 14:00 - 15:30, Bayside 103, Level 1
-
+
MS02.3 - Micro-RNA in Lung Cancer (ID 464)
14:00 - 15:30 | Author(s): U. Pastorino
- Abstract
- Presentation
Abstract
Lung cancer, for its high incidence and mortality, is the most common cause of death from cancer in many developed countries. In contrast to other cancers, there has been almost no improvement in the 5-year survival rates of lung cancer in the past 30 years, rate just above 10% in Europe, primarily because lung cancer is detected in most cases in an advanced stage. Detecting lung cancer at an earlier stage and, ideally, predicting who will develop the disease and particularly the most aggressive forms of cancer are the biggest challenge. Imaging via low-dose computed tomography (LDCT) scanning is being actively evaluated as a screening tool for early detection of lung cancer in high risk patients but, although the positive results in mortality reduction reported in the large NLST trial (1) were very promising, at present, the real efficacy of LDCT lung cancer screening in heavy smokers remains a controversial issue (2). Nonetheless, the high false positive rates of LDCT, leading to multiple screening rounds, the issue of over-diagnosis, the unnecessary and sometimes harmful diagnostic follow-up and the costs underscore the need for non-invasive complementary biomarkers for standardized use. MicroRNAs are small, non coding, endogenous single–stranded ribonucleic acids with regulatory functions that are involved in tuning of many important pathways, including developmental and oncogenic pathways. Because of their fundamental role in development and differentiation, their involvement in the biological mechanisms underlying tumorigenesis, as well as their low complexity, stability and easily detection, they represent a promising class of tissue and blood-based biomarkers of cancer (3). We explored miRNA expression profiles of lung tumors and normal lung tissues from cases with variable prognosis identified in a completed spiral-CT screening trial with extensive follow-up (4). We found a panel of deregulated miRNAs discriminating normal lung tissue versus lung cancer and significant association of miRNA expression profiles in both tumor and non-involved lung tissue with clinical-pathological characteristics of the patients such as tumor histotype, tumor growth rate, disease free survival. miRNA expression profile in tumor and normal lung tissues from patients identifed in the first two years of the screening, including mainly Stage Ia ADC with excellent survival, was found to be significantly different from the profile of subjects with more aggressive tumors appearing in later years of screening, independently from tumor Stage. Overall these results indicate that, both in tumors and in non involved lung tissues, miRNA signatures are able to discriminate patients according to tumor aggressiveness, independently from Stage and type. We have then investigated mirRNA profiles in plasma samples from cases and controls belonging to two independent LDCT screening trials with extensive follow-up where multiple plasma samples, collected before and at time of disease detection were available. We reported that miRNA profiling in plasma samples collected 1–2 yrs before the onset of disease, at the time of lung cancer detection by LDCT and in disease-free smokers, resulted in the generation of four miRNA signatures with strong predictive, diagnostic, and prognostic potential (4). Overall, these results suggest that plasma miRNA profiles might be helpful in pinpointing those early stage tumors at high risk of aggressive evolution that would need additional treatments. We recently completed a large validation study where the diagnostic performance of the plasma-based miRNA test was retrospectively evaluated in samples prospectively collected from smoker subjects within the MILD trial. In this study, 1,000 consecutive MILD plasma samples collected from June 2009 to July 2010 among lung cancer-free individuals enrolled in the trial and all patients with lung cancer diagnosed by September 2012 (n=85) were obtained. In patients we analyzed plasma samples collected both pre-disease (four to 35 months before lung cancer detection, median lag time of 15 months) and at the time of diagnosis. Custom-made microfluidic cards containing the 24 microRNAs composing the signatures identified in the exploratory study were created, and on each card eight plasma samples were analyzed per time. Since the goal of this study was to combine the plasma miRNA assay with LDCT results, in order to have a clinical useful tool to classify plasma samples, we developed a three-level miRNA signature classifier (MSC) of Low, Intermediate, or High risk of disease with subject categorization to one of these three risk groups based on pre-defined cut-points of positivity for the four different expression signatures of the 24 miRNAs previously identified. The results of this large validation study indicates that MSC is a significant diagnostic instrument for lung cancer detection with prognostic performance and support the combined use of MSC and LDCT to improve the efficacy of lung cancer screening (5). References 1. Kramer BS, Berg CD, Aberle DR et al. Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial (NLST). J Med Screen. 2011;18:109-111. 2. Pastorino U, Rossi M, Rosato V, Marchianò A, Sverzellati N, Morosi C, Fabbri A, Galeone C, Negri E, Sozzi G, Pelosi G, La Vecchia C. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012 May;21(3):308-15 3. Boeri M., Pastorino U. and Sozzi G. Role of MicroRNAs in Lung Cancer: MicroRNA Signatures in Cancer Prognosis. Cancer J. 2012 May;18(3):268-74 4. Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, Calabrò E, Croce CM, Pastorino U, Sozzi G. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8. 5. Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, Roz L, Conte D, Grassi M, Sverzellati N, Marchiano’ A, Negri, La Vecchia C, Pastorino U. Clinical Utility of a Plasma-based microRNA Signature Classifier within Computed Tomography Lung Cancer Screening: A Correlative MILD Trial Study. SubmittedOnly Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MS22 - The Mediastinum 2013 (ID 39)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Pulmonology + Endoscopy/Pulmonary
- Presentations: 1
- Moderators:F.J. Herth, C. Bai
- Coordinates: 10/30/2013, 14:00 - 15:30, Parkside 110 A+B, Level 1
-
+
MS22.4 - Surgical Techniques for Definitive Staging (ID 565)
14:00 - 15:30 | Author(s): U. Pastorino
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
O22 - Mesothelioma III (ID 122)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:P. Baas, R. Gaafar
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Gallery A, Level 1
-
+
O22.07 - Does surgery improve survival of patients with malignant pleural mesothelioma? A multicenter retrospective analysis of 1365 consecutive patients. (ID 2962)
16:15 - 17:45 | Author(s): U. Pastorino
- Abstract
- Presentation
Background
Medical management of malignant pleural mesothelioma (MPM) has obtained a moderate survival improvement over the years, while surgery with pleurectomy / decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option for selected patients with resectable disease. The aim of this study was to investigate the impact of surgical treatment on the outcome of patients with MPM.Methods
We retrospectively reviewed data from 1365 consecutive patients with histologically proven MPM, treated from 1982 to 2012 in six Institutions.Patients received either chemotherapy alone (n=172) or best supportive care (n=690) or surgical treatment (n=503), by either P/D (n=202) or EPP (n=301) with or without chemotherapy. All patients were followed up until death or for a minimum period of one year. The cox proportional hazards regression model was used to estimate relative improvements and to test the statistical hypothesis; a p-value less than 0.05 was considerd statistical significant.Results
Figure 1 Figure1. Kaplan-Meier survival curves according to the treatment (non surgical treatment vs EPP vs P/D) considering only patients with independent good prognostic factors After a median follow-up of 6.7 years (range 1.1-14.8), 230 (16.8%) patients were alive; median survival for patients who received palliative treatment or chemotherapy alone, P/D and EPP groups were 11.7 (95%CI: 10.5-12.5) months, 20.5 (95%CI: 18.2-23.1) months, and 18.8 (95%CI: 17.2-20.9) months, respectively. Testing the hypothesis of equal survival distributions the statistical significance was reached for the P/D and EPP groups versus non surgical treatment group (p <0.001) but not for the EPP versus P/D groups (p=0.885). The 30 day mortality was 2.6% after P/D and 4.1% after EPP (p=0.401). According to multivariate analysis (n=1227) age < 70, epithelial histology and chemotherapy were independent favourable prognostic factors. In the subset of 312 (25.4%) patients with all favourable prognostic factors median survival was 15.5 months after medical therapy alone, 19.4 months after P/D, and 18.7 months after EPP (Figure 1). A risk reduction of 31% (95%CI: 14-45%) for the P/D group and of 23% (95%CI: 7-36%) for the EPP group was observed compared to the medical treatment group.Conclusion
Our data suggest that patients with good prognostic factors had a similar survival whether they received medical therapy only, P/D or EPP. The modest benefit observed after surgery over medical treatment requires further investigation, and a large multicenter randomized trial, testing P/D after induction chemotherapy versus chemotherapy alone in MPM patients with good prognostic factors, is needed.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
