Virtual Library
Start Your Search
Patrick Micke
Author of
-
+
EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.01-15 - Systemic Hyperinflammation Is a Strong Independent Predictor of Early Mortality in Advanced NSCLC (Now Available) (ID 1143)
08:00 - 18:00 | Author(s): Patrick Micke
- Abstract
Background
Prognostic tools in NSCLC are important for treatment decisions and evaluation of new treatment options. Ample evidence support inflammation as a marker of outcome in NSCLC. Our study explores outcome for a population-based real-life cohort of patients in the highest stratum of inflammatory activity.
Method
The source cohort comprised all patients diagnosed with NSCLC between January 2016 – May 2017 at Gävle County Hospital, Sweden (n=155, inclusion rate 95%). Following exclusion of patients with active infection, the subgroup (n=77) in stage IIIB-IV with complete available laboratory parameters were studied further. Blood parameters were examined individually, and cut-offs (ESR>60 mm, CRP>20 mg/L, WBC>10 x10e9/L, PLT>400 x10e9/L) for high inflammation were set with an aim to pin-point the top echelon of hyperinflamed patients. A prognostic score was developed by assigning one point for each parameter above cut-off (0-4 points).
Result
One year survival of patients with an inflammation score of ≥2 (n=23) was 0% compared to 50% and 33% among patients with a score of 0 (n=36) and 1 (n=18), respectively (figure 1). The effect of a high inflammation score on overall survival remained significant in multi-variate analysis adjusted for confounding factors (stage, gender, age, smoking status, ECOG PS). The hazard ratio of an inflammation score ≥2 in multi-variate analysis (HR 3.45, CI 1.62-7.34) was on par with a change of ECOG PS from 0 to 2 (HR 3.67, CI 1.44-9.4).
Conclusion
Inflammation is a well established marker for treatment outcome in solid tumours. Our results show that high level inflammation is a strong independent marker for poor survival in patients with advanced stage NSCLC. This observation may indicate a need to stratify and subgroup patients in clinical studies with regard to systemic hyperinflammation and warrants further research on underlying mechanisms linked to tumour progression.
-
+
EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.04-18 - Real-World Treatment with Checkpoint Inhibitors: The Swedish Experience (Now Available) (ID 2590)
08:00 - 18:00 | Author(s): Patrick Micke
- Abstract
Background
The introduction of checkpoint inhibitors has fundamentally changed the treatment of advanced NSCLC patients.
Method
In order to evaluate if the encouraging results from clinical trials translates into the clinical routine and to confirm the value of biomarker testing we evaluated NSCLC patients that were treated with a checkpoint inhibitor in the Uppsala-Gävle health care region between Januari 2016 and October 2018. Latest patient follow up was done in March 2019. Patient information, including therapy, response rates and survival were obtained from patient records
Result
In total, 86 patients, were identified (44 female, median age 71 years; performance status 0=18, 1=45; 2-3=23). 28 patients were treated in the first line setting and 58 patients after previous chemotherapy. Checkpoint inhibitors that were given included pembrolizumab (31), nivolumab (36), atezolizumab (7). Two patients received a combination (durvalumab och tremelimumab).
67 of 86 patients were evaluable for response and of these 23 patients showed progressive disease, 17 stable disease, 22 partial response and 5 complete response. However, most patients that were not evaluable for response either had only 1-2 cycles because of severe side effects or died early independent from treatment. Thus, for all patient treated with at least one course of checkpoint inhibitors response rate were lower (SD:20%; PR:26% and CR:6%). PD-L1 analysis was done for 69/86 patients (80%). The response (PR or CR) was numerically higher in the group with PD-L1 positivity ≥1% or ≥50% than with negative PD-L1 expression (54% vs 47% vs 13%), although not statistically significant (p=0.11). Median overall survival for patients with PD-L1 <1% was 2.3 years, for patients PD-L1 ≥1% 2.7 years and PD-L1≥50% 3.9 years (log rank-test, p=0.95).
Conclusion
In conclusion, the response rates to checkpoint inhibitors in the first and second line were comparable to those observed in clinical trials. We confirmed that patients with low PD-L1 expression are unlikely to respond to checkpoint inhibition.
-
+
MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Yuko Minami, Mary Beth Beasley
- Coordinates: 9/10/2019, 11:30 - 13:00, Tokyo (1982)
-
+
MA18.05 - Diagnostic Difference Between Neuroendocrine Markers in Pulmonary Cancers: A Comprehensive Study and Review of the Literature (Now Available) (ID 171)
11:30 - 13:00 | Author(s): Patrick Micke
- Abstract
- Presentation
Background
The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non-small cell carcinomas (NSCC) is of high clinical relevance for prognosis and treatment. Diagnosis is based on morphology and immunohistochemical staining. The current WHO classification of lung tumors emphasizes synaptophysin and chromogranin A but also recommends CD56 as NE markers. The aim of the present study was to determine the diagnostic value of the insulinoma-associated protein 1 (INSM1) gene, in comparison with the established neuroendocrine markers, in pulmonary tumors.
Method
Tissue microarrays with tumor tissue from 54 resected pulmonary NE tumors and 632 NSCC were stained for INSM1, CD56, chromogranin A and synaptophysin. In a subset, gene expression data was available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 37 additional studies with data on NE markers in lung cancers from the last 15 years, whereof six with data on INSM1.
Result
Depending on cut-off level (1%+ or 10%+ positive tumor cells), the sensitivity and specificity for INSM1 to separate NE tumors from NSCC were 72-91% and 98-99%, respectively. In comparison, the sensitivity and specificity for CD56 were 85-89% and 96-98%, for chromogranin A 56-67% and 98-99%, and for synaptophysin 85-93% and 86-92%, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity (see table). INSM1 gene expression was clearly associated with NE histology.
Conclusion
The solid data of our investigation and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 or synaptophysin should be the first-hand choice to confirm high-grade NE pulmonary tumors.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.04-67 - Comparative Analysis of TMB and Mutations by Comprehensive Genomic Profiling (TSO500) in FFPE NSCLC Samples (ID 2106)
10:15 - 18:15 | Author(s): Patrick Micke
- Abstract
Background
Precision oncology for NSCLC involves an increasing number of targeted drugs and immunotherapy options. Comprehensive genetic profiling has been used in clinical studies to assess predictive biomarkers and mutation patterns, i.e. tumor mutation burden (TMB) associated with checkpoint therapy response. However, limited access to broader sequencing approaches, associated complex bioinformatic pipelines and issues with cross-platform reproducibility remain important hurdles for routine molecular pathology.
Method
Here we have used the novel TSO500 gene panel (523 genes, 1.95 Mb) on the NextSeq platform (Illumina) to analyze representative surgical FFPE NSCLC specimens (n=50). Detected mutations were evaluated in comparison to matched results from routine diagnostic sequencing based on a custom 18-gene HaloPlex panel (Agilent). Obtained TMB-scores will be compared to data from analysis with the FoundationOne CDx assay (work in progress).
Result
All 50 samples passed the pre-set QC filters. We found a wide range of TMB-values (0.79 to 610 non-synonymous mutations per Mb) with a median score of 5.6 mut/Mb (Figure 1). EGFR positive cases were found in the lower TMB range, while the remaining adenocarcinoma and squamous cell carcinomas were evenly distributed across the TMB spectrum. All known variants (n=105) from routine sequencing could be detected in the TSO500 data set (Illumina and in-house bioinformatic pipeline) with similar variant allele frequencies (r= 0.76).
Conclusion
Variant calling with regard to NSCLC hot-spot mutations seems to be robust, but the precision and performance of TSO500 outside clinical hot-spot regions remain to be established. The distribution of TMB scores in our series of NSCLC seems to be consistent with previously published data and concordance to results with FoundationOne CDx will be presented.
