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Daniel French
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MA15 - Usage of Computer and Molecular Analysis in Treatment Selection and Disease Prognostication (ID 141)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:John Le Quesne, Noriko Motoi
- Coordinates: 9/09/2019, 15:45 - 17:15, Tokyo (1982)
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MA15.09 - PD-L1 Status in Relation with Non-Small Cell Lung Cancer Major Subtypes, Differentiation, Molecular Profiling and Smoking History (Now Available) (ID 2874)
15:45 - 17:15 | Author(s): Daniel French
- Abstract
- Presentation
Background
Continued advances in lung cancer precision medicine have allowed targeted therapies based on an individual tumor’s genetic makeup. Recent advances in immune therapy based on immune checkpoint inhibitors have provided additional promising results. Currently, the majority of lung cancer mutational data available in the literature are from advanced stage non-small cell lung cancer. Mutational data from early stage lung cancer patients is limited. There is also limited data on PD-L1 tumor status is relation to mutational status along with other pathological and clinical characteristics. In this study, we evaluated these issues in 871 cases of surgically resected lung cancer.
Method
Multiplexed molecular profiling in 871 surgically resected lung cancer specimens was performed. A panel of genes including EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK was tested. Tumor PD-L1 status was also evaluated by immunohistochemistry using pharmDx22C3. PD-L1 status was measured by tumor proportional score (TPS): <1%, 1-49% and ≥50% tumor cell positivity. Correlations between PD-L1 and gene mutation status, smoking history, histological grade, gender and age of paraffin embedded blocks were analyzed.
Result
This cohort includes adenocarcinoma (68%), squamous cell carcinoma (SCC) (22%) and other subtypes (10%). The average age is 67. Females account for 52%. A positive smoking history was present in 93%. Well differentiated tumors (G1) account for 11%, moderately differentiated (G2) 37% and poorly and undifferentiated (G3) 52%. EGFR mutations were identified in 7.4% and KRAS mutations in 31.7%. TPS <1% accounted for 48.8%, 1-49% for 34.6% and ≥50% for 16.5%.
There was no statistically significant difference in PD-L1 TPS between histological subtypes or gender. Significantly more G1 tumors had a TPS <1% (76.7%) compared to G2 (57.4%, p=0.0013) and G3 tumors (41.8%, p<0.0001). Fewer G1 tumors had a TPS 1-49% (20.9%) than G2 (34.1%, p=0.015) and G3 (35.2%, p=0.01) tumors. G3 tumors were more likely to have a TPS ≥50% (24.6%) than G1 (2.3%, p<0.0001) and G2 (7.63%, p<0.0001) tumors. Never smokers were more likely to have a TPS <1% (71.1% vs 50.6%, p=0.04) and less likely to have a TPS ≥50% (5.8% vs 16.5%, p=0.04). Tumors with EGFR mutation were more likely to have a TPS <1% than those without EGFR mutation (70.7% vs 47.3%, p=0.0003) and less likely to have a TPS 1-49% (20.0 vs 35.5%, p=0.011). Tumors with KRAS mutations were less likely to have a TPS <1% (36.6% vs 54.9%, p<0.0001) and more likely to have a TPS 1-49% (40.6% vs 31.5%, p=0.0086) and ≥50% (22.8% vs 13.6%, p=0.0007). PD-L1 IHC performed on blocks stored for 2 years or longer had a statistically significant higher rate of TPS <1% compared to blocks stored for less than 2 years.
Conclusion
This study provides information relating to the relationship between PD-L1 levels and tumor molecular profile, histological grade and patient demographics. Additionally, we raise the possibility of false negatives on IHC performed for PD-L1 on paraffin embedded blocks stored for 2 years or more.
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OA01 - Advanced Diagnostic Approaches for Intrathoracic Lymph Nodes and Peripheral Lung Tumors (ID 117)
- Event: WCLC 2019
- Type: Oral Session
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Now Available
- Moderators:Marioara Simon, Tim Murgu
- Coordinates: 9/08/2019, 10:30 - 12:00, Melbourne (1991)
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OA01.02 - Endobronchial Ultrasound Staging of Operable NSCLC: Triple Negative Lymph Nodes May Not Require Routine Biopsy (Now Available) (ID 2621)
10:30 - 12:00 | Author(s): Daniel French
- Abstract
- Presentation
Background
Current staging guidelines with endobronchial ultrasound (EBUS) still recommend systematic biopsy of at least 3 mediastinal stations prior to surgical resection. Recently, a 4-point ultrasonographic score (Canada Lymph Node Score- CLNS) was developed to determine the probability of nodal metastasis in any given lymph node. A LN with CLNS<2 is considered very low probability for malignancy. We hypothesized that, during EBUS assessment of patients with cN0 non-small cell lung cancer, individual nodal stations that have CLNS<2 do not require routine biopsy because they are likely to represent true pN0 disease.
Method
The CLNS is a prospectively validated score that uses four ultrasonographic features to accurately predict LN malignancy. LNs were evaluated for ultrasonographic features at the time of EBUS and the CLNS was applied. “Triple Negative” LNs were defined as cN0 on CT (LN≤1cm), PET (no hypermetabolic activity) and EBUS (CLNS<2). Specificity, NPV, and false-negative rates were calculated against the gold-standard pathological diagnosis from surgically excised specimens.
Result
In total, 122 LNs in 58 cN0 patients were assessed. Triple Negative LNs were associated with the following T-stage distribution (T1a=12.07%, T1b=24.14%, T2a=34.38%, T2b=10.34%, T3=17.24%, T4=1.72%). Triple Negative LNs had a specificity, NPV, and false-negative rate of 86.10% (95%CI: 78.40-91.80%), 93.40% (95%CI: 86.90-97.30%), and 6.60%, respectively when using <2 as the CLNS malignancy cut-off. In total, only 5.74%(n=7) Triple Negative nodes were actually proven to be malignant, 6/7 (85.71%) on EBUS-TBNA, and 1/7 (14.29%) only after surgical resection.
Conclusion
Triple Negative LNs have a high NPV for malignancy. At the time of EBUS in cN0 patients, it may be possible that Triple Negative LNs do not require tissue sampling, thereby saving procedural time, cost, and discomfort. Findings also suggest that Triple Negative LNs with inconclusive biopsy results may not require repeat sampling. A prospective comparative trial is required to confirm these findings.
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