Virtual Library
Start Your Search
Scott Boerner
Author of
-
+
P2.03 - Biology (Not CME Accredited Session) (ID 952)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.03-03 - Upfront Next Generation Sequencing in NSCLC: A Publicly Funded Perspective (ID 11826)
16:45 - 18:00 | Author(s): Scott Boerner
- Abstract
Background
A growing number of targeted drug treatments in non-small cell lung cancer (NSCLC) have led to the need for molecular profiling beyond the standard of care (SOC) EGFR/ALK. Here we present actionable targets, impact on patient treatment, clinical trial opportunities and costs using the Illumina TruSight Tumor 15 panel (TST15) for NSCLC samples.
a9ded1e5ce5d75814730bb4caaf49419 Method
Tissue-based next generation sequencing using the TST15 was reflexively performed on all newly diagnosed cases of non-squamous NSCLC at the University Health Network (Toronto, Canada) from February 2017-February 2018. The panel identifies hot spot mutations in KRAS, EGFR, TP53, PIK3CA, BRAF, ERBB2, FOXL2, GNA11, GNAQ, KIT, NRAS, PDGFRA, RET, AKT1 and MET, but not fusions, copy number variations (CNV) nor MET exon 14 skipping mutations. Patient age, stage, pathologic subtype, and genotyping results were collected prospectively. Treatment changes as a result of TST15 and clinical trial opportunities (clinicaltrials.gov) were identified. Incremental testing costs were based on direct laboratory costs, but not personnel and administration costs.
4c3880bb027f159e801041b1021e88e8 Result
Testing included 342 samples from 336 patients. The TST15 panel identified 409 mutations from 342 samples. Sample demographics include: male: 53, and stage 1/2/3/4: 34/8/15/43%. Incremental actionable targets beyond EGFR and ALK were identified in 3.5% of patients (ERBB2 2.3%, BRAF V600E 1.2%). Most mutations occurred in TP53 (43%), EGFR (24%) and KRAS (26%). Co-mutations occurred in 32% (TP53, KRAS, EGFR) of samples. To date, one patient has had a treatment change as a result of TST15 beyond targeting EGFR. Above SOC clinical trial options were identified for 88% of stage IV and 26% of stage III patients. 3.6 samples were needed to identify one actionable mutation, predominantly in EGFR, at an estimated cost of $1919 CAD per target.
8eea62084ca7e541d918e823422bd82e Conclusion
Extended genotyping with TST15 in NSCLC identifies an additional 3.5% of patients with actionable mutations above SOC and improves clinical trial options for patients. Despite this, impact on patient treatment beyond targeting EGFR is minimal. To enhance the number of targets and minimize costs, affordable population-based comprehensive testing with a panel that includes fusions/CNV is needed.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P3.09 - Pathology (Not CME Accredited Session) (ID 975)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
-
+
P3.09-26 - Concordance of Surgical Resections and Fine Needle Biopsy-Derived Cell Block Sections for PD-L1 22C3 Immunohistochemistry (ID 13499)
12:00 - 13:30 | Author(s): Scott Boerner
- Abstract
Background
A significant proportion of lung cancer patients presents at an advanced disease stage. Diagnosis and treatment in these patients is frequently based on small tissue samples such as fine needle biopsies. Eligibility for pembrolizumab immunotherapy requires assessment of the PD-L1 expression. Data on the concordance of PD-L1 assessment by immunohistochemistry between quantitatively limited samples, in particular cytology specimens, and resections are scant. We studied PD-L1 in formalin-fixed paraffin-embedded (FFPE) cell block sections of CT-guided transthoracic fine needle biopsies in comparison with the subsequent resection specimens of the primary lung tumors.
a9ded1e5ce5d75814730bb4caaf49419 Method
Paired specimens of fine needle biopsy-derived cell blocks and subsequent lung tumor resections of the same anatomic site were obtained from the archives of the Department of Pathology, University Health Network. Cell blocks were produced from normal saline needle rinse fluids fixed with a final concentration of 10% neutral-buffered formalin and processed using the Histogel method for paraffin-embedding. Cytology samples treated with alcohol-based fixatives were not included. Cell block sections were reviewed for a minimum of 100 tumor cells. Cases below the cellularity threshold were excluded. Staining was performed using the 22C3 pharmDxTM assay (Agilent). All cell block and representative tumor sections were assessed by three observers (1 expert pulmonary pathologist, 2 cytopathologists). Tumor proportion scores (TPS) were recorded and a final TPS was determined using the mean between expert and second closest observer. Cases close to the ≥50% cut-off underwent multiheader microscope review. Pearson, intraclass correlation coefficients and test parameters were calculated using standard statistical methods.
4c3880bb027f159e801041b1021e88e8 Result
43 paired cases were informative. Mean interval between biopsy and resection was 1.5 months (range 0-4). TPS of cell blocks and resections showed positive correlation (Pearson: 0.8; range 0.78 - 0.84 for individual observers). Intraclass correlation coefficients were 0.97 (cell blocks) and 0.92 (resections). 10/43 (23%) cell blocks and 9 (21%) resections were positive at TPS≥50%. 21/43 (49%) cell blocks and 19 (44%) resections were positive at TPS≥1%. Sensitivity, Specificity, PPV, NPP and accuracy were 78/74, 91/71, 70/67, 94/77 and 88/72% for the ≥50/≥1% cut-off, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
Cytology FFPE cell block sections showed strong positive correlation with resection specimens of the same anatomic site for PD-L1 assessment using the 22C3 pharmDxTM immunohistochemistry assay. Reliability between observers was excellent. Test parameters, in particular for the ≥50% cut-off value, were deemed acceptable for clinical use. Selected slide review of cases with discordant scores indicated tumor heterogeneity as cause.
6f8b794f3246b0c1e1780bb4d4d5dc53
