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Johan Isaksson
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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
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EP1.01-15 - Systemic Hyperinflammation Is a Strong Independent Predictor of Early Mortality in Advanced NSCLC (Now Available) (ID 1143)
08:00 - 18:00 | Presenting Author(s): Johan Isaksson
- 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.
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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
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EP1.04-35 - Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) – Experiences from Clinical Practice – Sweden (Now Available) (ID 1002)
08:00 - 18:00 | Author(s): Johan Isaksson
- Abstract
Background
Lung cancer is the leading cause of cancer-related mortality worldwide, with NSCLC accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients (pts) with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated durable responses and represent the opportunity of a new treatment approach for pts with NSCLC.
Method
A chart review was conducted of incident cases of all pts who had been treated with immune check point inhibitor during the last 3 years in 4 hospitals. Data was retrospectively collected: pts characteristics, tumour characteristics, treatment details, tumor stage, adverse events, survival.
Result
In total, 244 pts, 114 (46.8%) males were given immunotherapy. Mean and median age was 70.11, 72.3 yrs. 219 (89.6%) were smoker or former smoker. 168 (68.9%) with PS 0-1, 61 (24.9%) PS 2. Most of the pts had stage IVA 119(48.6%), IIIB 34 (13.9%), IIIA 31 (12.7%). Adenocarcinoma in 151 (61.6%) and squamous cell carcinoma in 70(29.6%) of the pts. PDL1 < 1% in 30(12.2%), 1-49% in 66(27.3%) and >50% in 92 (37.6%). Pembrolizumab was given either as 1st or 2nd line in 120 (49.0%) ,nivolumab as 2nd, 3rd or 4th line in 85 (34.7%) and atezolizumab 31 (12.7%) as 2nd or 3rd line. 76(31.1%) had partial response,3 (1.2%) complete response, 41 (16.8%) stable disease, 64 (26.2%) progressive disease. 60 (24.5%) still on treatment. Most adverse events (AE) was pneumonitis 13 (5.2%), colitis 10 (4.1%), Thyroiditis 8 (3.2%).
Conclusion
Pembrolizumab has been given mostly in first line treatment due to high PD-L1 but nivolumab or tecentriq most in 2nd or 3rd line. Overall responses was 49.1%. Very few AE mostly pneumonitis and colitis
More data will be presented during the conference
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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
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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): Johan Isaksson
- 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.
