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K.S. Tan
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MA03 - Epidemiology, Risk Factors and Screening (ID 374)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:N. Bilir, H. Olschewski
- Coordinates: 12/05/2016, 14:20 - 15:50, Lehar 3-4
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MA03.08 - Quantifying Survival in Early-Stage NSCLC: Implications of Relative Survival vs Cause-Specific Survival (ID 6290)
15:14 - 15:20 | Author(s): K.S. Tan
- Abstract
- Presentation
Background:
Cancer-related mortality can be measured by two disparate methods: relative survival (RSR, observed survival of cancer patients versus expected survival of a matched population), and cause-specific survival (CSS, based on lung-cancer-specific mortality among cancer patients). Both are vulnerable to biases: RSR depends on a comparable reference population, while CSS relies on accurate cause-of-death coding. Regardless, RSR is more common in population-based studies as the cause of death is uninvolved. We apply both methods to the same dataset to assess their implications among early-stage NSCLC.
Methods:
Outcomes of patients diagnosed with stage I/II NSCLC (2000-2013) were obtained from the SEER registry. Five-year cumulative incidence of death (CID) is estimated by competing risk approach. Population-level mortality was extracted from the National Center for Health Statistics. The actuarial survival were summarized as RSR (Ederer II) and CSS, stratified by age at diagnosis and stage. In addition, the sensitivity of the methods is assessed by including patients with unknown cause of death in CSS (CSS-2).
Results:
Analyses included 15792 age <60 and 70789 age 60+ patients, with stage I (81%) or II NSCLC. Death with unknown cause was 5% of all deaths; 5-year CID for lung-cancer, other-known and other-unknown deaths were 43%, 14% and 2%. Lung-cancer 5-year CID increased with age, from 22% (age <44) to 47% (age 75+) among stage I, and 44% to 68% among stage II. CSS were greater than RSR in all cases. Although the bias was negligible for 1-year follow-up, the deviation increases with increasing age and years of follow-up. The estimated CSS-2s were always between RSR and CSS, suggesting that RSR underestimates the true lung-cancer-survival.
Conclusion:
In practice, RSR is appropriate for short follow-up and aggregate summaries, while caution is advised when reporting RSR by age groups for longer follow-up. Accurate assessment of the causes of death may alleviate such biases.Figure 1
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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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MA12.06 - Tumor Spread through Air Spaces (STAS) in Lung Squamous Cell Cancer is an Independent Risk Factor: A Competing Risk Analysis (ID 6051)
14:56 - 15:02 | Author(s): K.S. Tan
- Abstract
- Presentation
Background:
Tumor spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma, however, the incidence of and prognostic importance of STAS have not yet been defined in squamous cell carcinoma (SCC).
Methods:
In a cohort of 445 patients with p-stage I-III lung SCC, cumulative incidence of recurrence and lung cancer-specific death (LCSD) was evaluated by competing risks analysis and overall survival (OS) by Cox models.
Results:
76% of patients were >65 years of age. 273 patients died during follow up, one third (91, 33.3%) died of lung cancer whereas two thirds died of competing events or unknown cause. STAS was present in 132 (30%). The cumulative incidence of any, distant, and locoregional recurrence as well as LCSD were significantly higher in patients with STAS compared to those without STAS (Figure), whereas there was no statistically significant difference in OS. STAS was an independent predictor for both recurrence and LCSD in multivariable analysis (p=0.034 and 0.016, respectively, Table).
Conclusion:
STAS was present in one third of resected lung SCC and it was an independent predictor of recurrence and LCSD, supporting our proposal that STAS is a clinically important pattern of invasion and not an artifact. Figure 1 Figure 2
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MA12.08 - Clinicopathological Significance of Increasing Percentage of High-Grade Histological Subtypes in Lung Adenocarcinomas (ID 6023)
15:14 - 15:20 | Author(s): K.S. Tan
- Abstract
- Presentation
Background:
In early-stage lung adenocarcinomas, high-grade micropapillary (MIP) and solid (SOL) predominant pathology is known to be associated with worse prognosis. The aim of this study is, in addition to predominant patterns, to investigate clinical impact of the presence of small amounts (≥5%) as well as increasing percentage of high-grade patterns.
Methods:
Invasive tumors from early-stage lung adenocarcinoma patients who underwent curative-intent resection with no induction therapy were investigated (N=2017; 1995-2012) (8[th] edition TNM pStage I=1390, II=357, III=270). In 388 cases, synchronous lymph node (LN) metastases were available. Histological subtype (lepidic [LEP], acinar [ACI], papillary [PAP], MIP, or SOL) percentages were stratified into 4 groups; 0-4%, 5-24%, 25-49%, and 50-100%. The association between increasing percentage of patterns of primary tumor and the incidence of lymphatic/vascular invasion, necrosis, tumor spread through air spaces (STAS) as well as estimated 5-year cumulative incidence of recurrence (CIR) were analyzed. The differences in distribution of each pathological variable between 4 groups was analyzed by Chi-square test. The percentages of histological pattern were compared between primary tumor and LN metastasis.
Results:
Increasing percentage of MIP pattern is associated with increasing incidence of lymphatic/vascular invasion, STAS, as well as 5-year CIR (Figure 1a, p<0.001). Increasing percentage of SOL pattern is associated with increasing incidence of necrosis and 5-year CIR (p<0.001). Presence (≥5%) of SOL pattern is associated with higher incidence of lymphatic/vascular invasion and STAS (p<0.001) compared to the absence (<5%) of SOL pattern, but no significant relationship between lymphatic/vascular invasion and proportion of SOL pattern. The percentage of SOL pattern in LN metastasis is higher than that in synchronous primary tumors (Figure 1b).
Conclusion:
In early-stage lung adenocarcinomas, presence (≥5%) of MIP or SOL patterns as well as increasing percentages is associated with poor prognostic clinicopathological variables and incidence of recurrence. Figure 1
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OA01 - Risk Assessment and Follow up in Surgical Patients (ID 371)
- Event: WCLC 2016
- Type: Oral Session
- Track: Surgery
- Presentations: 1
- Moderators:W. Zhong, E. Lim
- Coordinates: 12/05/2016, 11:00 - 12:30, Schubert 2
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OA01.03 - Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Stage I NSCLC Patients: A Competing Risk Analysis (ID 4952)
11:20 - 11:30 | Author(s): K.S. Tan
- Abstract
- Presentation
Background:
At the time of diagnosis, two-thirds of patients with lung cancer are ≥65 years of age with significant comorbidities. We sought to determine the short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who underwent resection for stage I non-small cell lung cancer (NSCLC).
Methods:
Of 5371 consecutive patients who had undergone curative-intent resection of primary lung cancer (2000–2011), 2186 patients with pStage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were considered, including, Charlson comorbidity index, predicted postoperative (ppo) diffusion capacity of the lung for carbon monoxide (DLCO), and ppo–forced expiratory volume in 1 second (FEV1). Association between factors and cause-specific mortality was performed using competing risks approach.
Results:
Of 2186 patients, 1532 patients (70.1%) were ≥65 years of age, including 638 patients (29.2%) ≥75 years of age. In patients ≥65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer–specific CID, the higher noncancer-specific early-phase mortality was enhanced in patients ≥75 years of age compared with 65-74 years of age (Figure 1a). Multivariable analyses adjusted by age, sex, smoking status, comorbidities, tumor size, and surgical procedures showed that low ppoDLCO was an independent predictor for severe morbidity (p<0.001), 1-year mortality (p<0.001), and noncancer-specific mortality (p<0.001), whereas low ppoFEV1 for lung cancer–specific mortality (p=0.002). PpoDLCO can be used for estimation of 5-year cumulative incidence of noncancer death (Figure 1b, right, red curve) because of its linear relation, whereas ppoFEV1 for lung cancer-specific death (Figure 1b, left, black curve).
Conclusion:
In patients undergoing curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with increasing impact as patient age increases. Figure 1
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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): K.S. Tan
- 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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