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D.R. Aberle
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MINI 23 - Lung Cancer Risk: Genetic Susceptibility and Airway Biology (ID 135)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:P.E. Postmus, R. Young
- Coordinates: 9/08/2015, 16:45 - 18:15, 401-404
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MINI23.02 - COPD Severity by GOLD Status and Lung Cancer Risk: Results from a Large Prospective Screening Study (NLST-ACRIN Cohort Analysis, N=18, 714) (ID 865)
16:45 - 18:15 | Author(s): D.R. Aberle
- Abstract
Background:
Epidemiological studies consistently show that chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer among smokers. However, debate exists as to whether there is a linear relationship between the severity of COPD and risk of lung cancer. The National Lung Screening Study (NLST) and it’s sub-study by the American College of Radiology and Imaging Network (ACRIN), provides the means to re-examine these findings. We examined the effect of spirometry-defined COPD (according to GOLD status at baseline), on the risk of lung cancer in the NLST-ACRIN cohort (according to lung cancer incidence), in a large prospective lung cancer screening study of high risk smokers.
Methods:
In the NLST-ACRIN cohort of 18,475 screening participants eligible for the NLST, 6,436 screening participants had COPD (35%) according to baseline pre-bronchodilator spirometry and were followed for a mean of 6.4 years. From this group, 401 lung cancer cases were identified. The 6,436 screening participants with COPD were sub-grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1 (N=1607), 2 (N=3528), 3 (N=1083) and 4 (211). Lung cancer incidence at the end of follow-up was compared between the GOLD subgroups and those with normal spirometry (N=12,039).
Results:
Compared to those with normal spirometry, where the lung cancer incident rate was 4.63/1000 person years, the lung cancer incident rate was 7.58/1000 person years for GOLD 1, 9.43/1000 person years for GOLD 2, 12.7/1000 person years for GOLD 3 and 15.55/1000 person years for GOLD 4 (all P<0.0001). The lung cancer histology was significantly different, with more squamous and non-small cell cancers in those with COPD but more adenocarcinoma and Bronchoalveolar carcinoma in those with normal lung function (P<0.004). Figure 1
Conclusion:
In a large prospective study of unselected high risk smokers with and without COPD, we report a strong linear association between increasing severity of COPD and increasing lung cancer risk (incidence). This suggests that the risk of lung cancer is greatest in those with the most severe COPD and 3-4 fold greater than those with normal lung function. We also report that lung cancers of more aggressive histology were more common in those with COPD. Funding This study was funded by a grant from Johnson and Johnson and grants U01-CA-80098 and U01-CA-79778 to the American College of Radiology Imaging Network
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MTE 31 - Smoking Cessation Integrated with Screening (Window of Opportunity) (Ticketed Session) (ID 83)
- Event: WCLC 2015
- Type: Meet the Expert (Ticketed Session)
- Track: Prevention and Tobacco Control
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 07:00 - 08:00, 708+710+712
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MTE31.01 - Smoking Cessation Integrated with Screening (Window of Opportunity) (ID 2020)
07:00 - 08:00 | Author(s): D.R. Aberle
- Abstract
- Presentation
Abstract:
With the adoption of reimbursement for lung cancer screening in eligible beneficiaries both by third party payers and Medicare, smoking cessation becomes a strategic partner to reduce lung cancer mortality. In the present paradigm, Medicare will require screening programs to meet criteria of the American College of Radiology (or equivalent body) for radiologists, CT scanner platforms, and facilities; to satisfy specific patient eligibility criteria and shared decision-making; and to submit all screening data to a CMS-approved registry. Among the requirements is that the imaging facility or screening program make available smoking cessation interventions for current smokers. There are two basic approaches for this: [a] partnering in a transdisciplinary program that includes primary care, subspecialty care, and imaging in which counseling, shared decision-making, and smoking cessation programs are integrated and typically provided by the clinicians; or [b] building these services into an integrated screening facility with delivery by a qualified health care provider working in concert with the imagers. Some hybrid models have been described. Ultimately, the choice of approach is largely dependent upon institutional culture, institutional resources, and degree(s) of decentralization of the screening program. This session will introduce the benefits and liabilities of each approach as well as implications for costs
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ORAL 24 - CT Detected Nodules - Predicting Biological Outcome (ID 122)
- Event: WCLC 2015
- Type: Oral Session
- Track: Screening and Early Detection
- Presentations: 2
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ORAL24.05 - Reclassification of Lung Cancers Detected by CT Imaging in the American College of Radiology Imaging Network National Lung Screening Trial (ID 1454)
10:45 - 12:15 | Author(s): D.R. Aberle
- Abstract
- Presentation
Background:
The National Lung Screening Trial (NLST) found a 20% reduction in lung cancer-specific mortality using low dose CT vs chest radiography for screening. The magnitude of mortality benefit has been questioned given that a higher proportion of tumors in the CT arm were diagnosed as “bronchioloalveolar cell carcinoma”. Subsequent to the initiation of the NLST, the pathological classification of lung cancer was revised to take into account the reported favorable outcome for solitary in situ nodules <3 cm. The term “bronchioloalveolar carcinoma” (BAC) was eliminated in favor of the more explicit terms adenocarcinoma in situ (AIS), microinvasive adenocarcinoma (MIA), and invasive carcinoma with various predominant histological patterns. To better assess the impact of these recent changes in the Pathological classification of lung cancer on possible over-diagnosis in the NLST, we have reviewed the histology of lung tumors detected through the ACRIN-NLST trial and reclassified them according to the most recent WHO pathology classification.
Methods:
Histology was initially classified by the pathologists at sites where NLST participants were managed. Representative slides of 192 surgical resection specimens and 15 non-surgical biopsies from 207 patients were collected from 19 participating institutions. Digital images were prepared from 533 glass H&E stained slides using an Aperio digital slide imager. Digital images were examined by three pulmonary pathologists (WAF, DTM and JDH) and reclassified according to criteria and nomenclature of the recently published 2015 edition of the WHO classification.
Results:
There was 92% concordance between submitting and reference pathologists when cases were grouped into the broad categories of adenocarcinoma, squamous carcinoma, neuroendocrine and large cell lung carcinoma (LCLC). The WHO classification permitted a more detailed analysis of the tumors. Invasive adenocarcinoma was the largest tumor category comprising 61% (127) of all tumors and included 70 acinar tumors, 23 solid, 13 papillary, 8 micropapillary, 5 mixed mucinous/non-mucinous, 4 invasive mucinous, 3 lepidic and 1 adenocarcinoma that could not be further classified. There were 48 (23%) squamous tumors, 10 (5%) LCLC, 15 (7%) neuroendocrine tumors including 6 (3%) small cell lung carcinomas. Finally, one tumor had sarcomatoid histology and an additional tumor was classified at sclerosing pneumocytoma. On reclassification, only 5 of the 26 tumors originally referred to as BAC or as having BAC features by submitting pathologists met criteria for adenocarcinoma in situ or minimally invasive carcinoma. Twenty-one of these 26 tumors were reclassified as invasive adenocarcinoma, most frequently acinar pattern predominant (8 cases).
Conclusion:
Reclassification of tumors identified through low dose CT screening in the National Lung Screening Trial permitted a detailed analysis of histological features and should permit a more nuanced assessment of biology and prognosis of this important cohort than has been available to date. Reclassification of BAC mainly as invasive adenocarcinoma conflicts with the suggestion that much of the benefit in the NLST CT screening trial was derived from surgical removal presumably non-invasive low grade tumor. *ACRIN received funding from the National Cancer Institute through the grants U01 CA079778 and U01 CA080098.
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ORAL24.07 - Behavior Differences of Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial (NLST) (ID 587)
10:45 - 12:15 | Author(s): D.R. Aberle
- Abstract
Background:
Lung cancer screening identifies cancers with heterogeneous behaviors. In addition to screen-detected incidence lung cancers, screening also identifies prevalence cancers at the baseline screen and interval lung cancers diagnosed following a negative screen at any time point prior to the next screening round. To date, few studies have performed a comprehensive analyses comparing prevalence and interval lung cancers and screen-detected lung cancers based on sequence of screening results in the NLST.
Methods:
The entire CT arm of the NLST was reconstructed according to baseline and follow-up screening results (positive vs. negative screen). Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cancers (PC); interval cancers (IC) were defined as lung cancers diagnosed following a negative screen at any point prior to the next screening round. Two screen-detected lung cancer (SDLC) cohorts were identified based on one (SDLC1) or two (SDLC2) prior positive screens and two screen-detected lung cancer cohorts following one (SDLC3) or two (SDLC4) prior negative screens. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed.
Results:
Since there were no differences in patient characteristics and outcomes between SDLC1 and SDLC2 and between SDLC3 and SDLC4, the four screen-detected cancer case groups were combined into two combined SDLC case groups (SDLC1/SDLC2 and SDLC3/SDLC4). The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P < 0.001). PFS and OS were significantly lower for SDLC3/SDLC4 than SDLC1/SDLC2 (P < 0.004; P < 0.002, respectively). Overall, PFS and OS were highest in SDLC1/SDLC2 and lowest in the interval cancers (Figure 1); PFS and OS for the prevalence cancers were intermediate between SDLC1/SDLC2 and SDLC3/SDLC4. All findings were consistent when stratified by stage and histology. Multivariable Cox proportional models revealed that the SDLC3/SDLC4 case groups were associated with significantly poorer PFS (HR=1.72; 95% CI 1.19-2.48) and OS (HR=1.62; 95% CI 1.08-2.45) compared to SDLC1/2 lung cancers (HR=1.00). Figure 1
Conclusion:
This post hoc analysis reveals novel insight to the heterogeneity of lung cancers diagnosed in a screening population. As with interval cancers diagnosed following a negative screen, lung tumors that arise in a lung environment ostensibly free of lung nodules are likely more rapidly growing and aggressive which results in significantly poorer outcomes. Additional research will be needed to understand the potential translational implications of these findings and to reveal biological differences of screen-detected tumors.
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P3.06 - Poster Session/ Screening and Early Detection (ID 220)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.06-002 - Favourable Stage-Shift Limited to Screening Participants with COPD in a Biomarker Sub-Study of the National Lung Screening Trial (NLST) (ID 873)
09:30 - 17:00 | Author(s): D.R. Aberle
- Abstract
Background:
Based on a 20% reduction in lung cancer deaths in participants of the National Lung Screening Trial (NLST), CT screening for lung cancer is now widely recommended in the US. However concerns remain regarding the cost-benefits of screening due to overall low detection rates, over-diagnosis and high false-positive rates. Using the spirometric data available from the ACRIN-biomarker sub-study of the NLST (n=18,714), we examined the effect of Chronic Obstrucitve Pulmonary Disease (COPD) status on lung cancer detection in the NLST screening participants. Specifically we compared lung cancer incidence, histology and stage shift in those with and without COPD based on baseline pre-bronchodilator spirometry.
Methods:
Baseline spirometry results were available for 18,475 (99%) of the total cohort of 18,714, (6,436 with COPD and 12,039 with no COPD). Spirometry results were available for 758 (99%) of the 768 histology-confirmed lung cancer cases diagnosed over the 7 year follow-up period. After lung cancer cases were sub-grouped by spirometry-defined COPD (GOLD 1-4, n=401) and no baseline COPD (n=357) it was possible to compare the number of cancers, histology and stage according to screening arm. Differences in lung cancer incidence rates were compared by incident rate ratios, while prevalence, histology and stage shift, were compared by chi-square frequency tables.
Results:
In this NLST-ACRIN Biomarker sub-study, we found the demographic variables were comparable to those from the full NLST study. Regardless of screening interval, we found the lung cancer incidence was 2 fold greater in those with COPD compared to no COPD (P<0.0001). In those with COPD, we found a signficant reduction in adenocarcinomas and bronchioloalveolar carcinomas. After stratification by COPD status, when comparing CT versus CXR screening arms, we found no excess lung cancers and comparable lung cancer histology. However, a clinically significant stage shift favouring increased early stage (+17) and reduced late stage cancers (-23) was found (P=0.05). In contrast, in cancer cases with no COPD, we found an 18% excess of lung cancers in the CT arm (+29) which were of a BAC/AC histology. After correction for this overdiagnosis from these excess cancers, the stage shift no longer favoured early stage over late stage. Figure 1
Conclusion:
These data suggest that in those with COPD at baseline, CT screening (vs CXR) was associated with no excess cancers, no histology shift but a clinically significant stage shift favouring early over late stage cancers. In those with no COPD, CT was associated with excess cancers and a marginal stage shift.
