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MA09 - Lung Cancer Surgical and Molecular Pathology (ID 908)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Pathology
- Presentations: 1
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 202 BD
MA09.10 - Molecular Profiling and PD-L1 Status in 900 Cases of Surgically Resected Non-Small Cell Lung Cancer with Clinical and Pathological Correlation (ID 11188)
16:20 - 16:25 | Author(s): Wenda Greer
Precision medicine provides efficient treatment options for lung cancer patients as it targets the individual tumor’s genetic makeup. Recent development of immune therapy based on immune checkpoint inhibitor also provides hope for patients. Currently lung cancer mutational data available in the literature are mainly from advanced stage non-small cell lung cancer. There is insufficient information from early stage lung cancer patients. PD-L1 status in relation to clinical and pathological characteristics is also unclear. This study tried to address these issues from 900 cases of surgically resected lung cancer.a9ded1e5ce5d75814730bb4caaf49419 Method
Multiplexed molecular profiling in 900 surgically resected lung cancer specimens. A panel of gene including EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK was tested. PD-L1 was also evaluated by immunohistochemistry using pharmDx22C3. Tumor proportional score (TPS) in a 10% increment was measured. Mutational status and PD-L1 TPS in each cancer subtype in relation to cancer pathological characteristics were investigated. Correlations between gene mutation, PD-L1 status and cancer staging were performed. Gene mutation and PD-L1 status with patients’ demographic information such as gender, age, smoking history, as well as survival data after surgery were also analysed.4c3880bb027f159e801041b1021e88e8 Result
This cohort includes adenocarcinoma (65%), squamous cell carcinoma (24%), large cell carcinoma (6%), other subtypes (5%). Stage I accounts for 56%, stage II, 26%, stage III, 16%, stage IV, <2% with a mean age of 66 years. In adenocarcinoma, KRAS accounts for 36%, EGFR 10%, BRAF 1%, PIK3CA 1%, ALK 0.2%, no mutations 52%. Only 5% squamous cells carcinoma showed mutations.
PD-L1 TPS <1% accounts for (37%), TPS 1-9% (18%), TPS 10-19% (7%), TPS 20-29% (5%), TPS 30-39% (5%), TPS 40-49% (1%), TPS 50-59% (5%), TPS 60-69% (4%), TPS 70-79% (4%), TPS 80-89% (5%), TPS 90-99% (7%) and unsuccessful (2%). EGFR mutations were significantly associated with female (p<0.001) and never smokers (p<0.001), with well differentiated adenocarcinoma (p<0.001), and with absence of vascular invasion (p<0.01). KRAS mutations were more prevalent in younger age group (p=0.003). Poorly differentiated cancer histology was associated with absence of KRAS or EGFR mutations. There was no significant association between PD-L1 expression and age, sex, pathological stage and smoking status. PD-L1 expression was significantly associated with vascular invasion (p=0.035). EGFR mutations were significant associated with absence of PD-L1 expression (p=0.02), but no association between KRAS mutations and PD-L1 expression (p=0.10).8eea62084ca7e541d918e823422bd82e Conclusion
This study provides comprehensive information enhancing our knowledge in depth about driver gene mutations and immune checkpoint PD-L1 status in non-small cell lung cancer patients.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
- Presentations: 1
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
P3.13-31 - Creating a Precision Medicine Pipeline for Lung Cancers. (ID 14006)
12:00 - 13:30 | Author(s): Wenda Greer
The vision of High Mortality Cancer Precision Medicine Pipeline (HMCPMP) is to improve high mortality cancer outcomes. Our mission of HMCPMP is to establish precision medicine pipelines for high mortality cancers that start with the patient and ends with precise treatments for the patient based on their lung cancer’s unique molecular profile. HMCPMP leverages expertise areas of i) single-cell gene-discovery that allows for the identification of new barcodes and therefore new targets, ii) animal models that recapitulate human cancers, and patient-derived xenographs that allow for pre-clinical trials in mouse models to test novel drugs and drug development, iii) immunology and cancer stem cell biology to explore the role the immune system and stem cell niche impact tumourigenesis, iv) single-cell fluidics/3D organ systems that allow for understanding the heterogeneity of cancers and vi) data mining that allows for better treatment choices and the discovery of new treatment options based on their lung cancer’s barcodes.a9ded1e5ce5d75814730bb4caaf49419 Method
We have created a patient-centered precision medicine pipeline that moves resected lung cancers from the surgical suite to banking, through to single cell molecular diagnostics to validation (Figure 1).4c3880bb027f159e801041b1021e88e8 Result
Single-cell genomic profiling of resected lung cancers were prepared using a microfluidics platform Fluidigm C1 followed by transcriptome sequencing per single cell. We identified differentially expressed genes (DEGs) for stage, sex, and smoking status, followed by validation by quantitative PCR. We are currently pursuing new barcodes that differentially distinguish between the stratified subgroups of patients.8eea62084ca7e541d918e823422bd82e Conclusion
The significance of HMCPMP research is improved health, survivorship, and quality of life for people living with lung cancer. Although the economics of lung cancer are important and likely drivers of federal, provincial and regional research initiative, HMCPMP considers the human when faced with the diagnosis of lung cancer.
PAM is funded by the Dalhousie Medical Research Foundation and the Canadian Cancer Society6f8b794f3246b0c1e1780bb4d4d5dc53
Information from this presentation has been removed upon request of the author.