ECP 2023 Abstracts

S306 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Results: In 2017, 23% (825/3,652) of all NSCLC patients were tested for RET fusions, which increased to 32% (1,211/ 3,830) in 2019. This test was commonly performed sequentially in patients with wild-type EGFR and wild-type KRAS : 76% in 2017 and 55% in 2019. RET fusion testing was not performed for 759 (52%) patients in 2017 and 596 (37%) patients in 2019 despite being EGFR and KRAS wild-type. DNA FISH was the most frequently used test in 2017 (86%) and 2019 (48%), while RNA-based NGS increased from 6% in 2017 to 27% in 2019. The prevalence of a RET fusion was 2.4% (20/825) in 2017 and 1.2%(15/1,211) in 2019. Conclusion: The observed prevalence for a RET fusion in stage IV non-squamous NSCLC decreased from 2.4% in 2017 to 1.3% in 2019. This decrease may be a consequence of a change in test meth- odology from DNA-based FISH assays to RNA-based gene fusion transcript analysis. Furthermore, the data indicates that in 2019, 37% of patients were not tested for RET fusions despite a lack of driver mutations. Funding: This work was supported by Lilly, Roche, MSD, Astrazeneca and Pfizer. The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the abstract (All fees transferred to UMCG account) E-PS-15-008 Unravelling leukemic landscapes: cerebrospinal fluid-derived next generation sequencing analysis provides comprehensive diagnostic, therapeutic and prognostic perceptions O.C. Eren*, I. Kulac, T. Akan, O. Dogan, C. Aydin Mericoz *Koç University Hospital, Department of Pathology, Turkey Background & objectives: Cerebrospinal fluid (CSF) occasionally harbours the sole site of haematolymphoid malignancy recurrence. Our study emphasizes the value of Next Generation Sequencing (NGS) on CSF samples, especially in isolated central nervous system relapses, for crucial theranostic insights. Methods: Case 1: An 11-year-old male with B-cell precursor acute lymphoblastic leukaemia in remission exhibited numerous CSF blasts, while synchronous bone marrow biopsy and aspirate were unremark- able. Case 2: A 50-year-old male experienced CSF-confirmed recur- rence a year after localized myeloid sarcoma diagnosis and treatment. An NGS study using an RNA-based panel was performed on both CSF samples. Results: Case 1: NGS revealed ETV6-RUNX1 fusion, IKZF1 exon skipping deletion (exons 1-8), and PTPN11 point mutation (p.1472C>T; p.P491L). The patient had another CSF-based relapse one year post-chemotherapy. Case 2: NGS identified CBFB-MYH11 fusion and NRAS mutation (c.35G>A; p.G12D). The patient under- went allogeneic stem cell transplantation (allo-SCT) and has been in clinicopathologic remission for 12 months. Conclusion: IKZF1 deletion co-occurrence (case 1) may explain multiple relapses in a tumour with otherwise favourable prognosis due to ETV6-RUNX1 fusion. CBFB-MYH11 fusion (case 2) pro- vides valuable insight, indicating intrabdominal prevalence among myeloid sarcomas and predicting complete remission with aggres- sive therapy, supporting allo-SCT. NGS on CSF should be consid- ered for clinicopathological necessity as it enables evaluation of genetic transformations in hematopoietic tumours with sufficient CSF blast counts. E-PS-15-009 Robust validation and implementation of the C2i genomics whole- genome sequencing minimal residual disease assay for ultrasensi- tive ctDNA detection in liquid biopsy A. Erental*, T. Katz-Ezov, R. Tzabari, R. Campbell, U. Alon, D. Afterman, B. Oklander, A. Zviran, D. Hershkovitz *Tel-Aviv Medical Center, Israel Background & objectives: Accurate ctDNA detection is vital for MRD monitoring in solid tumours. Our goal was to implement and validate the highly sensitive C2i Genomics WGS MRD assay at Ichilov Medical Center’s Pathology Lab, utilizing patient-specific tumour sig- natures and sophisticated analytical techniques. Methods: Validation process included WGS of tumour tissue and germline peripheral blood mononuclear cells (PBMCs) for patient- specific signature identification and ctDNA WGS from blood samples for MRD detection. We sequenced 8 formalin-fixed paraffin-embedded (FFPE) samples, 12 reference plasma samples (6 healthy donors, 6 can- cer patients), and 15 contrived reference plasma samples with varying ctDNA dilution rates. Results: Our validation demonstrated 100% sensitivity and specificity on MRD positive and negative reference samples. The concordance in quantitative values of MRD, in terms of tumour fraction, was very high across dilutions spanning the aforementioned orders of mag- nitude. Mainly, a significant correlation (p-value < 0.01) of tumour fraction values among analytical samples processed at C2i Genomics and Ichilov was observed, indicating successful implementation and strong concordance with the reference lab. The established LLOD of 10e-4 matches that of the reference lab, with no ctDNA detection in control samples. The results indicate high reproducibility and robust- ness between sequencing labs. Conclusion: The validated C2i Genomics WGS MRD assay offers ultrasensitive ctDNA detection in liquid biopsies, enabling effective MRD monitoring in solid tumours, and providing valuable insights into disease progression and treatment response. The robust performance of this assay supports its application in clinical trials and routine clinical practice worldwide. E-PS-15-010 Implementation of the SOPHiA DDM™ homologous recombina- tion deficiency (HRD) solution to detect HRD in ovarian cancer tumours A. Erental*, A. Kaplan, C. Wizeman, R. Tzabari, L. Ifat, A. Mager, Y. Inbaram, D. Hershkovitz *Tel-Aviv Medical Center, Israel Background & objectives: Homologous recombination deficiency (HRD) is present in approximately 48% of ovarian cancer tumours. Some causes of HRD are well established, like BRCA1 and BRCA2 mutations, while others remain unknown. Here we describe the imple- mentation SOPHiA HRD Solution in our Lab. Methods: A set of 20 pre-characterized clinical samples in which the HRD status was determined in Myriad was used. DNA was extracted, libraries were prepared and sequenced. The validation process includes 13 samples that according to Myriad results expected to be BRCA positive & HRD positive samples, 4 BRCA negative & HRD positive samples and 3 BRCA negative & HRD negative. Results: Analysis of the validation cohort showed complete concord- ance with the Myriad results. At the time of writing the abstract, 32 clinical samples were received in the lab. Analysis showed that 3 samples were BRCA positive and HRD positive (9.3%), 4 were HRD positive BRCA negative (12.5%), 17 were HRD and BRCA negative (53.1%), 4 samples were BRCA negative and HRD status could not be determined (12.5%) and 4 samples failed (12.5%). Turnaround time for diagnosis was 14.5±7.5. Conclusion: SOPHiA HRD Solution combined the detections of HRR gene mutation and the Genomic Integrity Index in a single assay. In light of the validation results, it is suitable for clinical performance locally. There is a growing tendency worldwide to perform tests locally rather than outsourcing. This shortens TAT times and optimizes the process. Determining HRD status for ovarian cancer patients can help provide information regarding the potential benefit for PARP inhibitor therapy and bring help treatment decisions.