e15166 Background: CGP through Next-Generation Sequencing (NGS) has substituted single-gene testing to identify more druggable gene aberrations. The simultaneous detection of broad spectrum predictive biomarkers and molecular signatures including tumor mutational burden (TMB), microsatellite instability (MSI) burden, somatic BRCA, homologous recombination repair genes (HRR) and RNA variants by CGP provides a more cost efficient and tissue-preserving approach than serial single-biomarker analyses. Methods: 750 biopsy proven patients of various cancer spectrum at HCG cancer center were consented and profiled using Illumina TruSight Oncology 500 (TSO500) assay that interrogates 523 cancer-related genes on NextSeq in an IRB-approved prospective study. The findings were discussed in molecular tumor board (MTB) and recommendations from treating physicians were documented in patient records for change in clinical management and follow up. Results: A total of 1291 genomic alterations were detected in 750 cases (mean 1.7 mutations/sample). CGP identified genetic alterations with therapeutic and prognostic implications in 77% patients (Tier I- 34%, Tier II-64%, Tier III-14%). CGP revealed higher number of druggable genes (47%) than small panels (14%).Tumor agnostic markers for immunotherapy (IO) were observed in 20% of the current cohort, based on which IO was initiated and are on follow up. In 20% of the cohort, HRR pathway alterations including s BRCA (7%) were detected providing an option to treat with platinum or PARP inhibitors. Other significant alterations like EGFR, RAS/RAF, ERBB2, PIK3CA, cKIT, PDGFRA, ARID1A, ARID2, POLE, and FGFR were found. RNA sequencing yielded 54 RNA alterations (38 translocations and 16 splice variants). Androgen receptor splice variants were observed in 50% prostate carcinoma patients for whom taxane therapy was initiated. Other frequent fusions detected were: TMPRSS-ERG, RPS6KB1-VMP1, EML4-ALK, NTRK, PDGFRA and EWSR. Conclusions: CGP reports actionable and prognostic genetic alterations in 77% of patients who could potentially benefit by tumor-matched targeted and immunotherapy. Post MDT patients were assigned to approved therapies (5-80%) or change in clinical management (5-25%) based on the cancer type (Table). 25% patients were enrolled for investigator initiated clinical trials and are on follow up for clinical outcome and analysis of independent prognostic and therapeutic value of novel biomarkers in a larger cohort of Indian patient. [Table: see text]

e15020 Background: Neutrophil-Lymphocyte Ratio (NLR) and Lymphocyte-Monocyte Ratio (LMR) have been under scrutiny for their potential as a prognostic tool in various cancers. While there have been conflicting opinions on their reliability, NLR has shown rather near accurate predictions in previous studies. Targeted tyrosine kinase inhibitors have shown good results in improving OS and PFS of patients with EGFR-mutated NSCLC but the prognostic indicators are limited. This study aims to decipher if baseline NLR and LMR ratios are valid tools to predict prognosis of patients with EGFR-mutated NSCLC. Methods: We analyzed 78 advanced NSCLC patients harboring Exon 19 Deletion and Exon 21 L858R mutation undergoing EGFR-TKI therapy. Baseline NLR and LMR were measured in peripheral blood within two weeks prior to the initiation of TKIs. Overall survival was used as an outcome measure for TKI therapy and it is defined as from the initiation of TKIs to death by any cause. The cut-off for NLR and LMR was calculated using an X-tile plot (version 3.6.1, Yale University, New Haven, CT, USA) by dividing marker data into three populations: low, middle, and high (i.e., two divisions), with randomized 1:1 “training” and “validation” cohorts. Results: Overall median survival of the study group was 31.5 months and median age was found to be 60 years. Gefitinib (35.9%) and afatinib (34.6%) were the most commonly prescribed followed by erlotinib (21.8%) and osimertinib (7.7%). With cut-points of 1.8 and 4.9 we analyzed three populations for baseline NLR as ≤1.8, 1.9-4.9 and > 4.9. Similarly, for LMR cut-points of 3.49 and 5 were found and we analyzed patients with LMR of ≤3.49, 3.5-5 and >5. There was a statistically significant overall median survival observed as per the obtained NLR as well as LMR cut-off as given in the table. Conclusions: A statistically significant co-relation was observed with baseline NLR and LMR ratio in predicting response to EGFR TKIs in NSCLC. Our study further strengthens the concept of using NLR and LMR as peripheral blood biomarkers for prognostic assessment in cancer patients undergoing treatment.[Table: see text]

Background: Non-infectious granulomatous dermatoses involves a broad group of distinct reactive inflammatory conditions. They have overlapping morphological and clinical features and hence pose a diagnostic challenge to differentiate from other granulomatous dermatoses and affect the management of the patient. Aims and Objectives: To study the histopathological patterns of non-infectious granulomatous dermatoses and to correlate with clinical features. Materials and Methods: It is a retrospective study for a period of 5 years at a tertiary care centre in central Karnataka.Results: In the present study, out of 7273 skin biopsies there were 34 cases of non-infectious granulomatous dermatoses. Out of these 34 cases, granuloma annulare (50%) was the most common non-infectious granulomatous lesion followed by annular elastolytic giant cell granuloma (14%), foreign body granuloma (9%), tattoo granuloma (9%) perforating folliculitis (9%), xanthoma(6%) and xanthelasma (3%). Conclusion: Non-infectious granulomatous disorders of skin encompass a large group of disorders with overlapping features. Thus adequate clinical data and subtle histological findings are important for specific diagnosis which provides better patient management.

Background: Lung cancer is the poster child for advances in molecular oncology with a myriad of targeted therapies in NSCLC (non-small cell lung cancer) management. Kirsten rat sarcoma (KRAS) mutations are routinely isolated in NSCLC and account for a third of NSCLC oncogene driver tumors in Caucasian populations. The mutation is classically notorious to target with most therapies employed in management of KRASmut NSCLC being inhibitors of downstream signaling such as mitogen-activated protein kinase inhibitors (trametinib and selumetinib). There is a lacuna of information regarding prevalence and molecular epidemiology of KRAS mutations in NSCLC from an Indian context. Materials and Methods: The following study is a retrospective analysis of the incidence of KRAS epidemiology in high concentration epidermal growth factor receptor (EGFR) samples at a tertiary care hospital in South India from 2015 to 2017. Samples were selected following histopathological assessment and were subjected to nucleic acid extraction. KRAS mutation testing was performed using real-time polymerase chain reaction to ascertain the molecular epidemiology of KRAS in NSCLC patients. Results: KRAS mutations were observed in 15/44 NSCLC patients (34.09%) with a M:F ratio of 2:1. Majority of the mutations were single mutations, with 3 cases showing double mutations. Codon 12 mutations were observed in 6 cases followed by codon 146 mutations seen in 5 cases. Exon 3 (codon 59 and codon 61) and exon 4 (codon 117 and codon 146) were isolated in 5 and 3 cases, respectively. The current study demonstrated an elevated frequency for KRAS mutations in comparison to Asian cohorts. Conclusion: The advent of directly targeting KRAS inhibitors such as sotorasib (KRAS G12C inhibitor) necessitates KRAS mutation testing and warrants inclusion in the initial molecular workup of NSCLC.

Background: Large B-cell non-Hodgkin's lymphoma (NHL) comprises of a heterogeneous group of lymphomas with a high-grade morphology and aggressive nature. The diagnosis has gradually evolved from morphological characterization to classification of this group based on ancillary techniques such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular studies. Diffuse large B-cell lymphomas (DLBCL), not otherwise specified (NOS) is the most common B-cell NHL reported and a new diagnostic entity termed high-grade B-cell lymphoma harboring an MYC rearrangement with a BCL2 and/or BCL6 have been introduced by the WHO in 2017. MYC and BCL2/BCL6 proteins expression on IHC due to mutations leading to nuclear factor kappa B pathway activation is considered as double-expressor lymphoma (DEL). Materials and Methods: Sixty-two patients diagnosed with DLBCL, NOS on histopathology were subjected to IHC markers such as (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT, and Myc) and classified into activated B-cell and germinal center B-cell based on Hans' Algorithm. The samples were consequently subjected to tissue FISH for the detection of MYC, BCL2, and BCL6 gene translocations and classified as double-hit lymphoma (DHL)/triple-hit lymphoma (THL). The FISH results were subsequently compared for IHC expression of c-myc, Bcl2, and Bcl6. The staging, international prognostic index (IPI) scoring and lactate dehydrogenase levels were compared with progression-free survival (PFS) of 15 months among DHL/THL and DEL/TEL. Results: The median age of presentation among DLBCL-NOS patients is 58 years, while males (66.7%) were affected more commonly than females (33.3%). The majority of the patients presented with nodal involvement (71%) while extranodal involvement was seen in 29% cases. Hans' algorithm showed a significant P value with the IHC expression of BCL2, BCL6 and C-MYC. IHC and FISH correlation for BCL2 and BCL6 showed 100% sensitivity and 100% negative predictive value. IHC and FISH for c-MYC showed concordant results with a significant P < 0.03. The clinicopathological results of S/D/THL showed association with higher stage disease, higher IPI scoring, and high Ki-67 index with inferior PFS. Conclusions: IHC MYC is a sensitive screening modality for MYC translocation and can be used for the identification of rearrangement in lower socioeconomic areas. Based on clinicopathological studies, all patients with DLBCL must undergo MYC FISH testing as these patients behave as high-grade lymphomas. Hence, a new entity DLBCL with MYC rearrangement without BCL-2/6 rearrangements maybe considered as a novel entity and to be studied in future cohorts.