ECP 2023 Abstracts

S135 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Background & objectives: TruSight Oncology Comprehensive (TSO Comp) (EU) assay is a CE-marked comprehensive genomic profiling assay designed to interrogate solid tumours for small variants and gene amplifications from DNA, as well as gene fusions and splice variants from RNA. Methods: Accuracy and bridging studies to validate NTRK fusion CDx claims were conducted using banked formalin ‐ fixed, paraffin embed- ded (FFPE) clinical samples from patients enrolled in the larotrectinib clinical trials (NCT02122913, NCT02576431, and NCT02637687) supplemented with FFPE samples from various solid tumours. The agreement between results from TSO Comp and the reference method were compared to evaluate accuracy. Results: For accuracy, 407 samples were evaluable, of which 118 were CDx NTRK fusion positive and 289 negative by the orthogo- nal method; of which, 114 (out of 118) were CDx NTRK fusion positive and 273 (out of 289) negative by the TSO Comp assay. PPA was 96.6% (114/118, 95% CI: 91.5% to 99.1%) and NPA was 94.5% (273/289, 95% CI: 91.2% to 96.8%). Clinical effectiveness of the TSO Comp was assessed in the bridging study. For clinical efficacy, within the 164 patients in the larotrectinib extended efficacy analysis (ePAS4) population, 110 had samples available for TSO Comp test- ing and 97 yielded valid results. The ORR is 78.4% (76/97, 95%CI [69%, 86%]). Conclusion: Clinical efficacy of larotrectinib for the TSO Comp NTRK fusion positive population (97 patients, ORR=78.4%, 95% CI [69%, 86%]) was similar to the efficacy of larotrectinib in the total extended primary efficacy analysis population (164 patients, ORR=73%, 95%CI [65%, 79%]). Study results support the use of the TSO Comp (EU) assay to aid clinicians in identifying cancer patients with NTRK gene fusions who may be eligible for treatment with larotrectinib. PS-24-013 Lung cancer molecular approach by NGS/MPS: the experience of IAP‐PM using different NGS platforms V. Sousa*, A.F. Ladeirinha, A. Alarcão, M.R. Silva, T. Ferreira, C. Eliseu, M. Viseu, V. Almeida, R. Almeida, G. Fontinha, L. Carvalho *IAP-PM - Universidade de Coimbra, CHUC, Portugal Background & objectives: The identification of therapeutic targets is essential to guide the personalized treatment of lung cancer. Molecular tests and biomarkers evolution in lung cancer requires pathologists to be equipped with better and fast technologies. Methods: Since 2017, IAP-PM carried out NGS for mutation research in lung cancer. We started with ION PGM, used S5 from 2020 to 2021 and are currently using Genexus. Colon-Lung Panel was used on Ion PGM and S5, with manual library preparation. For Genexus we use Oncomine Precision Assay Panel, allowing DNA/RNA research simul- taneously, fully automated from library preparation to sequencing. Results: Of the 69 cases studied in the Ion PGM, mutations were found in 28.9% of the cases and only in samples with more than 10% of tumour cells. S5 allowed us to identify mutations in about 35% of the cases (18/51 cases) and we were able to detect mutations in samples with less than 10% of tumour cells. With Genexus, we were able to detect mutations in about 74% (142/192 cases) of the cases. We could detect mutations in cases with less than 10% of tumour cells and we have identified one target mutation in a case with only 2% of neoplastic cells and under 100 cells. Conclusion: Molecular biomarkers optimization is important in lung cancer, in order to obtain more complete information in a shorter time. Genexus, combined with Oncomine Precision Assay, has proven in our practice to be an effective technology for personalized therapy. Enhanced vision of molecular environment was achieved. The frequency of targetable mutations and complex mutation detection increased. The use of more sensitive technologies helps pathologists respond faster, more proficiently, with less likelihood of errors due to automation with less sample requirement. PS-24-014 Assessment of serummiRNA profiling in metastatic testicular cancer Z. Ujfaludi*, F.E. Fazekas, T.Z. Beöthe, T. Pankotai *University of Szeged, Albert Szent-Györgyi Medical School, Institute of Pathology, Hungary Background & objectives: As the long-term outcome of testicular can- cer depends on the formation of metastasis, the follow-up of patients and early diagnosis of such new lesions is essential. We studied the diag- nostic value of serum miRNAs in metastatic testicular cancer (MTC). Methods: Expression patterns of 10 miRNAs were determined by RT- qPCR in blood sera of healthy individuals and MTC patients (n=27+27) and matched surgically removed metastatic retroperitoneal lymph nodes (n=38), respectively. Using descriptive and mathematical-statistical meth- ods, the miRNA expression and clinical data of the patients were further analysed to evaluate the diagnostic value of our miRNA marker panel. Results: Determining the expression patterns of 10 pre-selected miRNAs from blood sera samples of healthy individuals and MTC patients (prior to surgical resection), we found that using the medians of either the over- all marker set or only of the 3 highest distinctive miRNAs, the 2 groups of the cohort can be separated with 93 and 96% probability, respectively. The expression patterns of the same miRNA markers in patient-matched metastatic lymph nodes do not correlate with the sera profiles in great concert with literature data nor reflect statistically significant differences between the subgroups of patients determined by histological evaluation. Conclusion: Our study showed that profiling the expression of 10 pre- selected miRNAs, healthy individuals and MTC patients can be distin- guished by high confidence. This method might have the potential for the follow-up of TC patients using regular minimal invasive blood test sampling. Although our findings are promising, expanding the cohort is necessary for further testing, strengthening, and possibly increasing the number of included marker miRNAs in developing a reliable clinical test. The project has received funding from the EU’s Horizon 2020 research and innovation program under grant agreement No.739593. Project no. TKP-2021-EGA-05 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. T.P. was funded by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/27/20 and UNKP-22-5-SZTE-318, UNKP-22-3-SZTE-274. PS-24-015 Comparison of data from two commercially available tissue-based comprehensive genomic profiling (CGP) solutions using AMP/ ASCO/CAP guidelines and ESMO ESCAT​ T. Wieland*, K. Hertel, M. Hiemenz, F. Fuhlbrück, J. Oughton, U. Schlecht, M. Cantone, S. Langer, H. Sorensen, D. Gonzalez de Castro, C. Messina, H. Adams *Foundation Medicine GmbH, Germany Background & objectives: We compared theoretical clinical signifi- cance data from two CGP solutions – the AVENIO Tumour Tissue CGP Kit (for Research Use Only) paired with navify Mutation Profiler (NMP), and TruSight Oncology 500 (TSO) assay paired with Pieri- anDx Clinical Genomics Workspace. Methods: AVENIO and TSO assays were run on 145 FFPE solid tumour samples (prostate: n=28; breast: 27; colon: 26; lung: 25 [among others]). Variant calls were acquired using manufacturer-provided soft- ware. Key variant annotation outputs were variant tiers and ESCAT guideline inclusion per tumour type. AMP/ASCO/CAP tiers were obtained with NMP for AVENIO or PierianDx for TSO. ESCAT inclu- sion was determined manually. Results: Tier I/II variants detected by both assays were: 643 short variants (SVs), 408 copy number alterations (CNAs) and 54 gene fusions. For ESCAT variants, none were missed by AVENIO.