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S. Lu
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MA12 - Miscellaneous Biology/Pathology (ID 476)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 2
- Moderators:B. Dome, W.D. Travis
- Coordinates: 12/06/2016, 14:20 - 15:50, Schubert 1
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MA12.05 - Can Tumor Spread through Air Spaces (STAS) in Lung Adenocarcinomas Be Predicted Pre- and Intraoperatively? (ID 6026)
14:50 - 14:56 | Author(s): S. Lu
- Abstract
- Presentation
Background:
We and others have reported the prognostic impact of tumor spread through air spaces (STAS) in lung adenocarcinomas. The goal of this study is to investigate preoperative predicting factors for STAS and to determine whether STAS can be detected by intraoperative frozen section analysis.
Methods:
In a cohort of 874 patients with small (≤2cm) stage I adenocarcinoma (1995-2012), we reviewed preoperative computed tomography (CT) and positron emission tomography (PET) scans. According to the 2016 Fleischner Society’s criteria, radiological whole tumor size, consolidation size, as well as C/T ratio (consolidation/whole tumor diameter) were determined using thin slice (<3mm) CT scans where available (n=174). Clinico-radiological prediction of STAS was evaluated by logistic regression model. Using the frozen section slides with adequate adjacent lung parenchyma surrounding tumor without artifact (n=48), the presence of STAS was evaluated by five pathologists who are unaware of the radiological findings or the pathological information on permanent slides. The kappa statistic was calculated to measure the agreement between two pathologists.
Results:
In univariable model for predicting STAS, current smoker, larger consolidation tumor size, C/T ratio, and SUVmax were significant variables. In multivariable model, current smoker and C/T ratio were independent risk factors for the presence of STAS (p=0.027 and p<0.001, respectively; Table 1a). The sensitivity and the specificity of frozen section for prediction of STAS were 71% (95% confidence interval: 52-91%), 92.4% (81-100%) respectively, and the accuracy was 80% (71-89%). The kappa statistics were 0.40-0.74 (Table 1b) with 8/10 being moderate or substantial agreement.
Conclusion:
Smoking status and C/T ratio were independent predictors for the presence of STAS in patients with small lung adenocarcinomas. Frozen section prepared with adequate surrounding normal lung tissue may help identify STAS intraoperatively. Figure 1
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MA12.10 - Histological Subtyping of Matched Primary and Metastases Sites in Lung Adenocarcinoma: Significance of Solid Predominance (ID 5767)
15:20 - 15:26 | Author(s): S. Lu
- Abstract
- Presentation
Background:
Clinical significance of 2015 WHO classification histological subtype of early-stage lung adenocarcinoma (LADC) has been well documented; the incidence and significance of histological subtypes in autologous metastatic tumors is unknown.
Methods:
Histological subtyping was performed on paired primary and metastatic LADC tumor samples from patients who underwent resection of metastases (N=203, 1996-2012). 57 cases with inadequate tumor specimen and 4 cases diagnosed as local recurrence were excluded.
Results:
Location of metastatic sites were – brain 51 (35.9%), lung 48 (33.8%), lymph node 14 (9.9%), pleura 10 (7.0%), and adrenal gland 5 (3.5%). Metastatic tumors demonstrated more frequent solid histological pattern than primary tumors (first predominance: 51% vs. 24%; second predominance 29% vs. 17%, Figure 1). Among all histological subtypes, solid subtype showed the highest concordance between primary and metastatic tumors (Figure 2). In addition, analysis of all available clinicopathological factors showed significantly higher percentage of solid subtype in both primary and metastatic tumors was observed in patients with smoking history (p=0.003 and p=0.004, respectively).
Conclusion:
Analysis of a large cohort of primary and autologous metastatic LADC tumors demonstrated a higher percentage of solid histological pattern metastases, even in cancers with a low solid component in the primary site of disease. Figure 1Figure 2
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OA07 - Lymph Node Metastases and Other Prognostic Factors for Local Spread (ID 376)
- Event: WCLC 2016
- Type: Oral Session
- Track: Surgery
- Presentations: 1
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OA07.06 - In Early-Stage Lung Adenocarcinomas, Survival by Tumor Size (T) is Further Stratified by Tumor Spread through Air Spaces (ID 5905)
15:15 - 15:25 | Author(s): S. Lu
- Abstract
- Presentation
Background:
We investigated whether tumor spread through air spaces (STAS) further stratifies survival beyond tumor size, T-descriptor independent of resection type (lobectomy or limited resection) and surgical margin.
Methods:
In patients with pT1a-T2bN0M0 lung adenocarcinomas (LADC, n=1399), tumor size, distance of STAS from the tumor, type of resection, surgical margin were evaluated. The patients with small (≤2cm) tumors were divided into STAS(-) (n=561) and STAS(+) (n=307) and their cumulative incidence of recurrence (CIR), and lung cancer-specific death (CID) were compared with patients with larger tumors (2-3cm, n=299) by use of competing risk analysis.
Results:
Of 1399 tumors, 521 (37%) were STAS(+). Compared to STAS(-), recurrence rates were higher with STAS(+) tumors even when the margin is ≥tumor size (Figure 1). In patients with ≤2cm STAS(+) tumors, CIR and CID are higher than in patients with larger (2-3cm) tumors (Figure 2). The poor prognostic influence of STAS(+) was evident even when analyzed by the procedure or recurrence pattern (Figure 2 table).
Conclusion:
STAS further stratifies survival beyond tumor size, T-descriptor in early-stage (pT1a-2b) lung adenocarcinoma based on the higher prognostic potential for recurrence and lung cancer-specific death independent of the type of resection or margin. Figure 1 Figure 2
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OA12 - SBRT and Other Issues in Early Stage NSCLC (ID 383)
- Event: WCLC 2016
- Type: Oral Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:D. De Ruysscher, M.R. Mueller
- Coordinates: 12/06/2016, 11:00 - 12:30, Strauss 2
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OA12.05 - Noninvasive CT-Based Image Biopsy System (iBiopsy) for Early Stage Lung Adenocarcinoma (ID 6080)
11:45 - 11:55 | Author(s): S. Lu
- Abstract
- Presentation
Background:
CT screening programs frequently detect early stage lung adenocarcinoma. Recent studies show that distinct subtypes of lung adenocarcinoma are associated with different prognosis and suggest that treatment should be tailored to histological subtypes as identified in the new WHO Lung Tumor Classification. To develop this personalized approach, it is important to have reliable tools to diagnose tumors before treatment, preferably non-invasively through image analysis. We have developed a CT-image analysis system (iBiopsy) that uses computerized deep learning and artificial intelligence. To validate the accuracy of a noninvasive CT-based image biopsy system (iBiopsy) in differentiating early stage lung adenocarcinoma subtypes of atypical adenomatous hyperplasia (AAH), adenocaricnoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC).
Methods:
We retrospectively identified 365 eligible patients from Zhongshan Hopsital Fudan University, diagnosed with AAH, AIS, MIA or IAC by surgical pathological diagnosis. The last high definition CT scan prior to the surgery of the lesion was analyzed using the iBiopsy system, blinded to pathological result. Based on a pulmonary nodule image feature set (PNIFS) in combination with classified pattern models, such as R-SVM, all the pulmonary nodules were classified into four groups. For diagnosis efficacy, area under the curve (AUC) of Precision-Recall score (PRS), receiver operating characteristic (ROC) of a classification model were calculated in each group.
Results:
365 patients were included in the analysis. The classification recognition rate of the PNIFS was 80.03%. The average value of PRS is 0.92, the mean of ROC is 0.95, and it is more than 0.80 for the cross validation value.
Conclusion:
iBiopsy system allows the non-invasive imaged based stratification of pulmonary adenocarcinoma nodules into four groups, from AAH to IAC. Our result suggest that iBiopsy system could ultimate facilitate the diagnosis and precision management of pulmonary nodules.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-084 - Implications of 8th Edition TNM Proposal: Invasive vs. Total Size for T Descriptor in pT1a-2bN0M0 Lung Adenocarcinoma (ID 5788)
14:30 - 14:30 | Author(s): S. Lu
- Abstract
Background:
The aim of this study was to conduct a clinicopathological comparative analysis of total tumor versus invasive tumor size in pT1a-2bN0M0 nonmucinous lung adenocarcinomas.
Methods:
Resected pT1a-2bN0M0 lung adenocarcinomas (1995-2012) based on 8th edition of TNM classification using total (N=1475) and invasive tumor size (N=1482) were included. Recurrence free probability [RFP] and lung cancer-specific survival [LCSS]) were compared between both pT-staging systems using Kaplan-Meier method.
Results:
Use of invasive size for the T descriptor increased the number of pT1a tumors by 2 fold compared to use of total tumor size (316 vs. 161), with no difference in RFP and LCSS (RFP, 82% vs. 80%; LCSS, 94% vs. 93%). Use of invasive rather than total size also showed better stratification of lymphatic/vascular invasion and high-grade histological subtypes according to increasing pT stage. RFP and LCSS in invasive-size-based pT2b were lower than those in total-size-based pT2b (RFP, 44% vs. 60%; LCSS, 69% vs. 77%).
Conclusion:
In pT1a-2bN0M0 nonmucinous lung adenocarcinoma, the 8th edition TNM proposal to use invasive rather than total size for the pT descriptor gives better prognostic discrimination by capturing a larger number of patients with favorable prognosis (pT1a) and providing better stratification for pT2b. Figure 1 Figure 2
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-050 - Elevated Expression of CCP Genes is Associated with Absolute Chemotherapy Benefit in Early Stage Lung Adenocarcinoma Patients (ID 4204)
14:30 - 14:30 | Author(s): S. Lu
- Abstract
Background:
A validated RNA molecular expression signature based on cell cycle progression (CCP) genes [CCP score] and a molecular Prognostic Score [(mPS) combination of CCP score and pathological stage] are significant prognostic markers of cancer-specific mortality in patients with early stage lung adenocarcinoma. Additionally, preliminary data suggest a significant association between CCP score and absolute benefit with platinum-based adjuvant chemotherapy in early stage lung adenocarcinoma patients. The aim of this study is to further demonstrate the effectiveness of CCP score and mPS in predicting platinum-based chemotherapy benefit in a large, multi-institutional cohort of stage IB and IIA lung adenocarcinoma patients who underwent definitive surgical resection with and without adjuvant chemotherapy.
Methods:
Formalin-fixed paraffin-embedded surgical tumor samples from approximately 1000 patients diagnosed with stage IB and II adenocarcinoma who underwent definitive surgical treatment with adjuvant platinum-based chemotherapy (n = 400) and without (n = 600) will be analyzed for 31 proliferation genes by quantitative RT-PCR. The associations of CCP score and mPS with absolute benefit from platinum-based chemotherapy will be separately examined using Cox proportional hazards regression with an outcome of 5-year lung cancer survival.
Results:
To date, lung tumor samples have been accrued from 388 patients treated with a platinum-based chemotherapy and 590 untreated patients. We hypothesized that the absolute treatment benefit will increase as CCP score or mPS increases. Results will be shown for continuous CCP score and mPS as well as pre-defined binary CCP score and binary mPS.
Conclusion:
This study will determine the abilities of CCP score and mPS as predictive tools for absolute chemotherapy benefit and 5-year lung cancer survival in patients with early stage lung adenocarcinoma thereby furthering the clinical utility for these signatures to identify patients with high risk disease who should receive adjuvant chemotherapy.
