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Jhingook Kim
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-14 - Impact of Smoking on Treatment Outcome in Early Squamous Cell Lung Cancer (T1N0) (ID 13823)
16:45 - 18:00 | Author(s): Jhingook Kim
- Abstract
Background
Smoking is the major risk factor for squamous cell lung cancer. However, squamous cell lung cancer in never-smoker is known to have poor survival outcomes. We compared clinicopathologic features and outcomes between smokers and never-smokers in resected early squamous cell lung cancer (T1N0).
a9ded1e5ce5d75814730bb4caaf49419 Method
An institutional database was reviewed retrospectively between 1994 and 2016 (N = 445). Eligible patients included completely resected squamous cell lung cancer, less than 3 cm in tumor size, and without N1 or N2 involvements. Patients were stratified by gender and smoking status.
4c3880bb027f159e801041b1021e88e8 Result
423 (95%) smokers and 20 (5%) never-smokers were identified. The median age of never-smokers was 66 years (range, 39 - 83), and 11 of these patients were female (55%). The median age of smokers was 66 (range, 42 - 84), and most of them were male (97.9%). The T stage were distributed equally in both groups. In smokers, 84 (19.9%) patients experienced recurrence whereas only 1 patient (5%) of never-smokers occurred distant metastasis (p < 0.001). Distant metastasis was most frequent recurrence pattern in smokers (n= 40), but locoregional recurrence also a fairly frequent pattern (n = 30). The 5-year overall survival rates and recurrence free survival rates were 70.9% and 61.5% in smokers and were 64.1% and 64.1% in never-smokers respectively (p = 0.65, and 0.34, respectively).
8eea62084ca7e541d918e823422bd82e Conclusion
There was no significant differences in clinicopathologic features and outcomes between smokers and never-smokers in early squamous cell lung cancer.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.13-29 - Patient-Derived Xenograft Models(PDX) of Lung Squamous Cell Carcinoma(SCC) for Preclinical Studies (ID 14278)
12:00 - 13:30 | Author(s): Jhingook Kim
- Abstract
Background
Non-small cell lung cancer is the most prevalent type of lung cancer, and one of its subtype, squamous cell carcinoma has limited targeted therapeutic options in comparison with adenocarcinoma. For this reason, we established the patient-derived xenograft models of primary lung cancer and then focused on the SCC PDX models to be used for the discovery of target mutations through the molecular profiling of lung tumors and their association of therapeutic responses
a9ded1e5ce5d75814730bb4caaf49419 Method
PDX models were established using the tissues of patients who underwent surgery as primary lung cancer at Samsung Medical Center during the period between October, 2014 and September, 2017. Briefly, tumor tissues from patients were subcutaneously engrafted and passaged two more times in NOD-scid-IL2Rγnull mouse. Then we are analyzing histological characteristics and molecular profiles of established SCC PDX by whole exome sequencing and whole transcriptome sequencing.
4c3880bb027f159e801041b1021e88e8 Result
Mutation profiles of squamous cell carcinoma Patient Tumors and their PDX models Patient tumor
PDX
ID
Gene
Mutation
Frequency
Gene
Mutation
Frequency
PDL-040
HRAS
JAK1
PTEN
TP53
GNAQ
U2AF1
G13V
N136fs
-78fs
Y236C
T96S/M59L
G167C
1.000
0.397
0.488
1.000
0.143/0.080
0.080
PDL-041
CTNNA2
FRG1
M672I
C159Y
0.278
0.042
PDL-089
EP300
AMER1
RB1
EP300
AMER1
RB1
0.473
0.576
0.500
AMER1
RB1
EP300
R142K
I425fs
G438V
0.851
0.472
0.479
PDX-073
PDX-079
DNMT3A
BRAF
TP53
FRG1
F571L
V600E
R249S
Q137K
0.606
0.524
0.571
0.521
BRAF
TP53
FRG1
DNMT3A
V600E
R249S
Q137K
F571L
0.377
1.000
0.026
0.444
PDX-100
DDR2
BRAF
GNAS
TP53
E757D
G469A
Q286P
156_157RV>L
0.484
0.388
0.583
0.671
BRAF
DDR2
TP53
GNAS
G469A
E757D
156_157RV>L
Q286P
0.941
0.212
0.500
0.180
PDX-114
PDX-186
KEAP1
PIK3R1
L281M
M200fs
1.000
0.464
PDX-190
PDX-205
PDX-207
TP53
ATRX
C176F
S1944R
0.617
0.537
TP53
C176F
1.000
PDX-231
MET
STK11
KEAP1
RPSAP58
GNAS
L829V
D115N
G333C
Q113H
V57M
0.494
0.410
0.551
0.426
0.488
KEAP1
MET
STK11
GNAS
RPSAP58
SMO
G333C
L829V
D115N
V57M
Q113H
R138L
1.000
0.485
1.000
0.318
1.000
0.400
PDX-252
HLA-A
HLA-A
HLA-A
HLA-A
HLA-A
HLA-A
TSC1
FRG1
ATRX
EEF1B2
R38W
G80R
A114D
S129P
T187P
T187R
S487C
Q137K
Q929E
R122H
0.500
0.267
0.617
0.611
0.091
0.231
0.293
0.026
0.870
0.227
PDX-271
TSC1
KDR
M322T
V297I
0.357
0.300
PDX-302
JAK1
TP53
E667Q
N268I
0.514
0.488
PDX-318
ARID1A
NF1
TP53
FRG1
SMO
SOX17
TRRAP
H203Q
R2556T
LRKKGEPHH289fs
A151G
F332fs
R147L
A598V
0.125
0.168
0.472
0.048
0.456
0.200
0.349
PDX-364
TSC2
T927I
0.575
PDX-366
KDR
TP53
NOTCH1
FRG1
A1103D
V173L
L107F
Q137K
0.494
0.609
0.600
0.496
NOTCH1
TP53
FRG1
CHD4
KDR
L107F
V173L
Q137K
R1825L
A1103D
0.160
1.000
0.035
0.061
0.270
PDX-372
CDKN2A
TP53
D33H
A161fs
0.377
0.534
CDKN2A
TP53
D33H
A161fs
1.000
0.461
PDX-402
PIK3CA
FRG1
FRG1
FRG1
V344G
L150S
A151T
C159Y
0.503
0.443
0.445
0.455
PIK3CA
GNAQ
FRG1
V344G
T96S
C159Y
0.173
0.098
0.050
PDX-409
DNMT3A
KEAP1
KMT2D
F511L
G158C
P1912fs
0.653
0.467
0.669
KEAP1
KMT2D
GNAQ
FRG1
DNMT3A
G158C
P1912fs
T96S
C159Y
F511L
0.917
0.446
0.063
0.043
0.460
PDX-410
TP53
KEAP1
KEAP1
C124G
G480V
G186R
0.564
0.585
0.737
KEAP1
KEAP1
TP53
G480V
G186R
C124G
0.298
0.656
1.000
PDX-415
DNMT3A
NFE2L2
NFE2L2
CREBBP
TP53
APC
CDKN2A
I247F
R18Q
D11N
S2356F
R337L
ENDNG1530fs
R52fs
0.494
0.584
0.568
0.600
0.469
0.559
0.531
AMER1
AMER1
APC
CDKN2A
CREBBP
NFE2L2
NFE2L2
TP53
DNMT3A
FLT3
H619R
H619N
-1530fs
R52fs
S2356F
R18Q
D11N
R337L
I247F
M799I
0.703
0.698
0.478
0.462
1.000
0.364
0.250
1.000
0.628
0.076
PDX-420
HLA-A
NOTCH1
TP53
K292E
G427C
H179R
0.067
0.575
1.000
PDX-434
NOTCH2
RRAS2
KEAP1
KMT2D
TP53
V968L
Q72L
Y54F
D4400fs
P301fs
0.366
0.422
0.512
0.509
0.482
IGF1R
KEAP1
NOTCH2
TP53
RRAS2
P266S
Y54F
V968L
P301fs
Q72L
0.204
1.000
1.000
0.477
0.792
PDX-454
TNFAIP3
R52T
0.431
NF1
TNFAIP3
TP53
LTTILKN58fs
R52T
P152fs
0.476
0.458
0.455
PDX-473
CREBBP
FLT3
Q913R
I920V
0.410
1.000
PDX-480
TSC2
NF1
NF1
NF1
TP53
RRAS2
EEF1B2
V1695E
N793S
K798Q
F1287L
R158L
Q143R
R122S
0.831
0.169
0.160
0.210
0.828
0.034
0.166
NF1
TP53
TSC2
W784L
R158L
V1695E
0.838
0.875
0.516
In PDX models of 49 patients, successful lung SCC PDX engraftment and identical histomorphology was achieved. And the 30 sets of exome sequencing analyses showed that the somatic mutations were relatively preserved. Among them, some interesting targetable mutations including BRAF(V600E) were identified. We identified consistency of transcriptome profiles of PDX models during the passages.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.16-41 - Postoperative Pembrolizumab for the Patients with Pathologic Stage I Adenocarcinoma with Solid or Micropapillary Pattern (ID 14418)
12:00 - 13:30 | Author(s): Jhingook Kim
- Abstract
Background
Prognosis of surgically resected stage I adenocarcinoma was relatively fair with up to 75% of 5 year disease free survival rate. However, in some cases, in spite of the very small-sized tumor, recurrence as systemic metastasis is found. Solid or micropapillary subtype adenocarcinoma are reported as poor prognostic subtypes, additional treatment after surgical resection for those subgroup was required to improve survival. We reported that incidence of PD-L1 strong positivity is significantly higher in solid-predominant subtype of adenocarcinoma, PD-L1 inhibitor can be more effective adjuvant treatment modality in those subtype.
a9ded1e5ce5d75814730bb4caaf49419 Method
Design: Open-label, single arm, single center, phase 2 trial. (NCT03254004)
Eligibility: The subject must have primary lung adenocarcinoma with stage I and less than 4 centimeter, whose tumor should be solid-predominant or micropapillary (>5%) by postsurgical pathological examination.
Objective: The primary objective of this study is to assess the improvement of disease-free survival rate by adjuvant therapy with pembrolizumab for solid or micropapillary adenocarcinoma with pathologic stage I and tumor size less than 4 cm. The secondary objective is to assess the safety profile of adjuvant pembrolizumab in adjuvant setting.
Treatment: Pembrolizumab 20mg IV infusion every 3 weeks for 12 months until disease progression or prohibitive toxicity. The treatment should be started within 8 weeks after surgery.
Statistics: The hypothesis is that adjuvant pembrolizumab will improve 3-year disease-free survival from 65% to 80% in pathologic stage Ia lung adenocarcinoma patients with solid/micropapillary subtypes. Assuming that the subject enrollment period is 1.5 years, follow-up of last registered subject period is 4 years, and the disease free survival period follows the exponential distribution, a significance level 5% (one side) and 63 peoples are required 85% at the power of test. At this time, assuming that the dropout rate is 10%, it is necessary to register 70 subjects
Assessment : Chest CT (covering up to both adrenals) will be done every 3 months till 1 year since the study treatment, and then every 4 months afterward till 2 years and thereafter every 6 months till 3 years. Brain MRI and bone scan will be done at 1 year and 2 years since the study treatment. This study is an investigator-initiated trial with support from MSD.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
6f8b794f3246b0c1e1780bb4d4d5dc53