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Edouard Auclin

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OA09 - Prevention and Cessation (ID 909)

Event: WCLC 2018
Type: Oral Abstract Session
Track: Prevention and Tobacco Control
Presentations: 1

Moderators:
Coordinates: 9/24/2018, 15:15 - 16:45, Room 205 BD

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OA09.06 - Molecular Alterations and Estimated Indoor Radon in NSCLC Patients from the French National Cancer Institute Registry: Radon France Study (ID 14168)

16:10 - 16:20 | Author(s): Edouard Auclin

Abstract
Presentation

Background

Radon is a radioactive gas, considered the leading cause of lung cancer in non-smokers. We assessed the correlation between the radon exposure areas in France and the molecular alterations nationally registered in non-small cell lung cancer (NSCLC) patients.

a9ded1e5ce5d75814730bb4caaf49419 Method

We retrospectively collected all NSCLC tested for EGFR, BRAF, HER2 and KRAS mutations (m) and ALK and ROS1 rearrangements (r) on the 28 French Plateform led by INCa (French National Cancer Institute). The prevalence of molecular alterations by region was correlated to the indoor radon risk area based on the official French (Institut de Radioprotection et de Sûreté Nucléaire, INSN, France). Paris and its region Ile-de-France were not included in this analysis due to its high rate of patients that are native from other regions.

4c3880bb027f159e801041b1021e88e8 Result

116.424 NSCLC were included. Overall, KRAS was positive in 27,7% (27.314/98.522), EGFR in 11,27% (13.125/116.424), ALK in 3,2% (2.928/91.291), BRAF in 2,3% (2.419/105.919), ROS1 in 1,12% (373/33.222) and HER2 in 0,8% (816/97.749) of all cases.

We stratified the French regions in 3 areas based on their exposure to radon: high (Auvergne-Rhône-Alpes, Bretagne, Normandie, Pays de la Loire), intermediate (Bourgogne-Franche-Comté, Nouvelle Aquitaine, Occitanie, Provence-Alpes-Cote-d'Azur) and low explosure (Centre Val-de-Loire, Grand Est, Hauts de France). The prevalence of driver alterations (EGFR, BRAF, HER2 and ROS1 were significantly higher in high exposure area. The prevalence of KRAS mutations was significantly higher in low exposure area.

	Low risk	Intermediate	High	P
EGFR mutation	1962 (10%)	4338 (11%)	4176 (11.4%)	<0.0001
ALK rearrangement	577 (3.3%)	1019 (3%)	896 (3%)	0.35
BRAF mutation	327 (1.8%)	830 (2.4%)	692 (2.4%)	0.0001
HER2 mutation	109 (0.6%)	266 (0.9%)	252 (0.8%)	0.01
ROS1 rearrangement	61 (0.9%)	133 (0.9%)	126 (1.3%)	0.005
KRAS mutation	4717 (29.8%)	9215 (28.2%)	7895 (27%)	<0.0001
Molecular drivers*	3037 (3.9%)	6587 (4.4%)	6142 (4.4%)	<0.0001
* EGFR, BRAF & HER2 mutations, ALK & ROS1 rearrangements; KRAS mutation excluded.

8eea62084ca7e541d918e823422bd82e Conclusion

NSCLC molecular alterations that are linked to low tobacco consumption were higher in the French region with high radon exposure. Role of the radon in lung cancer carcinogenesis of specific molecular subtypes should be further explored.

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Information from this presentation has been removed upon request of the author.

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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

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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P1.01-68 - Correlation of the Lung Immune Prognostic Index (LIPI) and PDL1 Status with Outcomes for Immune Checkpoint Inhibitors in Advanced NSCLC Patients (ID 14256)

16:45 - 18:00 | Author(s): Edouard Auclin

Abstract

Background

Baseline LIPI, based on derived NLR (neutrophils/[leucocytes-neutrophils]) and lactate dehydrogenase (LDH) was associated with outcomes for immune checkpoint inhibitors in advanced NSCLC patients. We assessed the correlation between LIPI and PDL1 for ICI outcomes in NSCLC.

a9ded1e5ce5d75814730bb4caaf49419 Method

Baseline dNLR and LDH and clinical data were retrospectively collected in advanced NSCLC patients, treated with PD1/PDL1 +/- CTLA4 inhibitors from Nov. 2012 to Mar. 2018, in a multicentric cohort (N=794) from 11 centers. LIPI stratified 3 groups: good (dNLR<3+LDH<upper limit of normal (ULN), intermediate (dNLR>3 or LDH>ULN), poor risk (dNLR>3+LDH>ULN). PDL1 positivity was defined as ≥ 1% tumor cells expression by immunohistochemistry.

4c3880bb027f159e801041b1021e88e8 Result

476 patients (60%) were male, 693 (87%) smokers, 695 (88%) had PS ≤1, with median age 65; 576 (73%) had nonsquamous histology. PDL1 was ≥ 1% in 195 (70%) patients, negative in 82 (30%), and unknown in 517. The median of prior lines was 1 (0-11). The median PFS and OS were 4 months (m) [95% CI 4-5] and 12 m [10-15]. dNLR was>3 in 276 (35%) and LDH>ULN in 290 (37%) patients. LIPI stratified 349 patients as good (44%), 323 (41%) as intermediate and 121 (15%) as poor LIPI risk groups. LIPI was an independent factor for OS (table) and PFS (HR 2.58; CI 1.3-5.2, P=0.02). ≥ 1% PDL1 and ≥ 50% PDL1 were not correlated with OS and PFS. Median OS for good, intermediate, and poor LIPI risk groups were 21 m [17-23], 11 m [9-14] and 4 m [2-6], respectively (P=<0.0001). Median PFS for good, intermediate, and poor risk was 5 m [5-7], 4 m [3-5], and 2 m [1-3], respectively (P=0.0005). No differences were observed in LIPI groups according to the PDL1 expression.

Multivariate analysis for OS

95% CI

P value

Immunotherapy line

2.117

0.641

6.992

0.219

N# Metastasis sites

≥2

1.242

0.727

2.121

0.428

Performance status

≥2

2.141

1.059

4.332

0.034

Albumin

>35 g/dL

0.867

0.507

1.48

0.6

LIPI

Intermediate

Poor

1.697

4.178

0.917

1.956

3.142

8.925

0.001

PDL1 IHC

≥1%

0.713

0.406

1.252

0.239