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Wen-zhao Zhong
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ES06 - Perioperative Therapy for Early Stage NSCLC (ID 221)
- Event: WCLC 2020
- Type: Educational Session
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 14:15 - 15:15, Scientific Program Auditorium
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ES06.03 - Neoadjvuant and Adjuvant Targeted Therapies (ID 4048)
14:15 - 15:15 | Presenting Author(s): Wen-zhao Zhong
- Abstract
- Presentation
Abstract not provided
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MA02 - Technological Advances in Diagnostics, Imaging and Therapeutics for Lung Cancer (ID 103)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Diagnostics and Interventional Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 14:15 - 15:15, Scientific Program Auditorium
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MA02.08 - Computed Tomography Attenuation Value as Considerable Predictor for Malignancy in Clinical T1 Lung Adenocarcinoma (ID 1611)
14:15 - 15:15 | Author(s): Wen-zhao Zhong
- Abstract
- Presentation
Introduction
To explore the quantitative variables of thoracic computed tomography for predicting the pathologic malignancy of cT1 lung adenocarcinoma.
Methods
We retrospectively collected data from 96 consecutive patients with clinical T1 lung adenocarcinoma. -160 Hu was used as the cutoff of solid and ground glass opacity portion. AAH, AIS, MIA and LPA were considered as less malignant (LM), while other subtypes of IACs were included into more malignant (MM) group.
Results
The area under receiver operating characteristic curves of m-CT value, D_solid, D_whole, Area_solid, Area_whole, 1D_CTR and 2D_CTR were respectively 0.89 (95%CI, 0.81 ~ 0.97; Se=83%, Sp=93%), 0.895 (95%CI, 0.832 ~ 0.958; Se=88%, Sp=79%), 0.736 (95%CI, 0.634 ~ 0.839; Se=87%, Sp=60%), 0.89(95%CI, 0.82 ~ 0.96; Se=87%, Sp=81%), 0.738 (95%CI, 0.634 ~ 0.841; Se=83%, Sp=63%), 0.861 (95%CI, 0.780 ~ 0.942; Se=90%, Sp=74%), 0.869 (95%CI, 0.788 ~ 0.949; Se=85%, Sp=84%). Multiple logistic regression revealed that mean CT value was the independent risk predictor of more pathologically malignancy of clinically T1 lung adenocarcinoma (p=0.003).
Table1: Clinicopathological comparison between the less malignant and more malignant groups Less malignant(n=43) More malignant(n=53) p value Age, years, mean 56.12 65.38 <0.001 Gender >0.05 Male 13 22 Female 30 31 Loaction >0.05 RUL 21 19 RML 3 3 RLL 7 12 LUL 7 10 LLL 5 9 D_solid(mm) 2.18 13.32 <0.001 D_whole(mm) 16.84 23.13 <0.001 Area_solid(mm²) 8.73 122.32 <0.001 Area_whole(mm²) 187.44 322.56 <0.001 1D_CTR 0.13 0.56 <0.001 2D_CTR 0.07 0.35 <0.001 2D m-CT Value(Hu) -629.40 -348.55 <0.001 EGFR Mutation >0.05 Mutation 19 25 Wild type 18 25 ALK Mutation >0.05 Mutation 0 2 Wild type 30 43 D_solid: the longest diameter of the solid portion in the greatest horizontal section of nodule; D_whole: the longest diameter of the greatest horizontal section of nodule; Area_solid: the area of the solid portion in the greatest horizontal section of nodule; Area_whole: the area of the greatest horizontal section of nodule; 1D_CTR: D_solid/D_whole; 2D_CTR: Area_solid/Area_whole; m-CT value: mean CT attenuation value of the greatest horizontal section of nodule. mm: millimeter; CTR: consolidation tumor ratio. Hu: Hounsfield unit. Table2: Univariate and multivariate analysis for predicting the more pathologically malignant cT1 lung adenocarcinoma. Univariate analyses Multivariate analyses Category odd ratio 95% CI p value odd ratio 95% CI p value Age continuity 1.075 1.032~1.119 <0.001 1.019 0.955~1.088 0.56 Gender Male vs Female 0.611 0.261~1.428 0.255 D_solid(mm) ≤3.473 vs > 3.473 29.593 9.624~90.996 <0.001 6.086 0.079~469.082 0.415 D_whole(mm) ≤14.807 vs >14.807 10.05 3.686~27.402 <0.001 14.991 0.635~353.753 0.093 Area_solid(mm²) ≤6.513 vs >6.513 28.75 9.517~86.850 <0.001 0.258 0.10~6.642 0.413 Area_whole(mm²) ≤156.641 vs >156.641 8.25 3.201~21.265 <0.001 0.336 0.017~6.748 0.476 1D_CTR ≤0.124 vs >0.124 27.927 8.862~88.011 <0.001 0.546 0.015~19.903 0.741 2D_CTR ≤0.040 vs >0.040 25.143 8.526~74.148 <0.001 4.232 0.454~39.442 0.205 m-CT Value(Hu) ≤-494.927 vs >494.927 65.185 16.481~257.815 <0.001 19.723 2.783~139.780 0.003 95%CI: 95% confidential index; mm: millimeter; CTR: consolidation tumor ratio. Hu: Hounsfield unit.
Conclusion
Mean CT attenuation value is useful for predicting the higher pathologically malignant degree of clinical T1 lung adenocarcinoma. M-CT value is a potential reference factor for the formulation of surgical procedure for cT1 lung adenocarcinoma.
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MA12 - Controversies Old and New (ID 230)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA12.10 - Treatment and Survival Differences in Patients with Large Cell Neuroendocrine Carcinoma of the Lung: A SEER Database Analysis (ID 3389)
16:45 - 17:45 | Author(s): Wen-zhao Zhong
- Abstract
Introduction
Large cell neuroendocrine carcinoma of the lung (L-LCNEC) is a rare but highly aggressive tumor. We aimed to determine the differences in treatment and survival in L-LCNEC and to identify predictors for survival using Surveillance, Epidemiology, and End-Results (SEER) data.
Methods
Data of patients diagnosed with L-LCNEC in 2004–2015 were retrieved. Age, sex, race, and tumor site, size, grade, and stage were evaluated. Multivariable logistic and Cox regression were performed to identify factors associated with overall survival (OS) and cancer-specific survival (CSS).
Results
Figure 1. Effect of treatments in patients with large cell neuroendocrine carcinoma of the lung
Table 1. Univariate and multivariate analyses of overall survival (OS) in the eligible patients.
A total of 2,838 eligible cases were enrolled at the time of L-LCNEC diagnosis. In total, 1,774 (62.5%), 796 (28.0%), and 268 (9.5%) patients were diagnosed at the ages of 60-79, <60, and ≥80 years, respectively. L-LCNEC incidence (83.6%, N=2,373) was significantly high among Caucasians. Most tumors were in the right (56.2%, N=1,594) upper (53.5%, N=1519) lung lobe. Grade III (34.7%) and stage IV (49.0%) diseases were commonly detected in men (56.1%). Old age (60-79 years, hazard ratio [HR] [95% confidence interval]: 1.352 [1.136-1.609], P=0.001; ≥80 years, 1.841 [1.313-2.582], P<0.0001), stage III (2.053 [1.371-3.074], P<0.0001) and IV (3.878 [2.595-5.796], P<0.0001), and tumor size >5 cm（1.391[1.071-1.808], P=0.013） were independent unfavorable prognostic factors. Surgery (0.553 [0.397-0.770], P<0.0001) and chemotherapy (0.455 [0.392-0.528], P<0.001) were significant independent favorable prognostic factors. Patients treated with surgery, chemotherapy, or surgery plus chemotherapy had the lowest distant metastases rates.
Conclusion
We provide population-based estimates of the incidence and prognosis of L-LCNEC. Surgery and chemotherapy significantly improved the OS and CSS of patients with L-LCNEC.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.60 - FLAIR: Phase II Study of Osimertinib plus Bevacizumab versus Osimertinib in Advanced NSCLC Patients with EGFR L858R Mutation (ID 3221)
00:00 - 00:00 | Author(s): Wen-zhao Zhong
- Abstract
Introduction
The 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib monotherapy has been considered as the new standard of care for advanced EGFR mutated non-small-cell lung cancer (NSCLC) patients. However patients with L858R mutation have achieved lower efficacy of EGFR-TKIs than those with 19Del mutation, even with osimertinib. Herein to improve the efficacy of L858R population is still unmet medical needs. While CTONG1509 study has presented the addition of bevacizumab to 1st generation EGFR TKI erlotinib appears to significantly improve L858R patients’ progression free survival the combination of osimertinib and bevacizumab is worth deep exploration.
Here we present the rationale and study design for the FLAIR trial, a multicenter, open label, randomized, phase II study.
Methods
Study entry will be limited to adults aged ≥ 18 years with primary recurrent or metastatic nonsquamous non-small-cell lung cancer with documented an EGFR exon 21 L858R mutation. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until disease progression or unacceptable toxicity.
The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of overall response (DoR), time to treatment failure (TTF), overall survival rate at 2 years, and safety and tolerability.
In the HR assumption of 0.65, sample size of 90 patients is driven by the needs of 67% statistic power for the test at the significance level of 0.2, two sided, with the accrual period of 8 months and the longest follow-up of 32 months.
The first analysis (primary analysis) data cut-off (DCO) point will be happened when 70% data maturity for PFS based on investigator assessment (according to RECIST 1.1) has been reached (depending on the actual event rate).
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P85 - Targeted Therapy - Clinically Focused - MET (ID 262)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P85.02 - NGS could not Replace FISH Regarding to MET Amplification as an Optimal Biomarker (ID 1581)
00:00 - 00:00 | Author(s): Wen-zhao Zhong
- Abstract
Introduction
MET amplification (MET amp) is known as an important mechanism of resistance to EGFR-TKIs in NSCLC. We investigated the association between survival benefits and MET status identified by different methods, to explore the appropriate biomarker to select patient for MET-TKIs treatment in advanced NSCLC.
Methods
Method: FISH (fluorescence in situ hybridization), IHC (immunohistochemistry) and NGS (next generation sequences) were performed prospectively from FFPE/liquid samples with NSCLC. MET amplification by FISH was defined as MET/CEP7 ratio＞2 or CN(copy number )＞6 and served as the standard reference for over-express by IHC and copy number gain (CNG) by NGS. Objective response (OR) and PFS were used to confirm optimal biomarker for MET inhibitor.
Results
We identified MET dysregulation of 37 NSCLC patients by FISH, IHC and NGS before MET-TKIs administration and assessing the survival benefits of 33 cases treated MET inhibitor. The consistence of FISH, IHC and NGS was only 54%. They are the different population. MET amplification identified by FISH proved the best predictive efficiency for survival benefits. The PR rate was 82% (18/22) and median PFS was 4.8 months in MET amp, compared to 1.0 months for cases with non-MET amp (P= 0.004). Both MET dysregulations identified by NGS or IHC failed to distinguish the significant survival difference in patients with MET-TKIs. Comparing with MET amplification by FISH, effective cases were more seen in patients with CNG > 4.0 or IHC score ＞290 . Based on these two cut-off values：CNG > 4.0 or IHC score ＞290 still did not predict efficacy of MET inhibitors, suggesting CNG by NGS had no significant associations with efficacy benefits.
Conclusion
Compared to MET amplification identified by FISH, CNG dysregulation by NGS or MET protein over-express by IHC could not serves as the predictive biomarker for MET inhibitors.
