1078 Background: Androgen receptor (AR) expressing triple negative breast cancer (TNBC) is a sub-set of TNBC with an evolving prognostic and predictive behaviour. AR immunohistochemical threshold for positivity has not been standardized and a wide range of cut-offs have been used across studies ( > 0% to 75%). In this study we explored AR immunohistochemistry thresholds in relation to disease free survival (DFS) and clinical outcomes in non-metastatic TNBC using the Allred and H-Score systems. Increasing interest in AR as a therapeutic target for TNBC and the use of digital tissue image analysis makes it important to standardize AR immunohistochemistry reporting. Methods: 100 FFPE (formalin-fixed paraffin-embedded) tumour blocks were retrieved for non-metastatic TNBCs diagnosed between January 2015 and May 2017 and immunostained using AR441 (IgG1) mouse monoclonal antibody. Clinical follow-up ranged from 59 to 31 months and DFS was calculated. Cut-off scores were explored using Evaluate Cutpoints ( R maxstat package) and X-tile software. The score with maximum split in DFS (based on log-rank statistics and lowest p-value) was chosen as the cut-off. Descriptive and survival statistics was performed. Results: The median age was 51 (SD 11.262; range 28 to 82) years. Using Evaluate Cutpoints ≥3 was found as the threshold for AR by Allred Score. 36% cases were AR positive using Allred score (HR 0.508; CI 0.234 - 1.11; p-value 0.08). Using Evaluate Cutpoints ≥30 was found as the threshold for AR by H-Score (HR 0.624, CI 0.306 - 1.27; p-value 0.19). 35% cases were AR positive using H-Score. X-tile analysis also found the cut-offs as ≥3 and ≥30 for Allred and H-Score respectively (p < 0.05). A significant correlation was seen between the two scoring systems (Pearson Correlation 0.935; p < 0.01). A significantly higher number of grade III TNBCs were AR negative (n = 55/76) compared to grade II (n = 9/24) (p = 0.002). Cut-off for Ki67 was 75 (HR 1.61, CI 0.85-3.04, p-value 0.141) with a significantly higher number of AR negatives in the Ki67≥75 group (21/26; p < 0.05). The overall median DFS was 51.9 months. There was no significant difference in DFS for the AR negative (median: 47.4 months; mean: 39.39 months) and AR positive (Median survival not reached; mean: 41.3 months) groups(p = 0.23). Conclusions: AR immunohistochemistry cut-offs using the Allred (≥3) and H-Score (≥30) are close to the ones used for ER/PR immunohistochemistry as per ASCO/CAP guidelines, making a strong case for universal application of these systems for harmonization of AR data.
e12579 Background: Metaplastic breast carcinoma is a rare histological subtype that has basal like characteristics and is reported to have a poorer prognosis than no specific type/ductal carcinoma (ductal/NST). We aimed to investigate clinicopathological features and outcome from a single institution based registry. Methods: Clinical records of breast cancer patients treated during 2012-2019 were screened and 31 cases of metaplastic breast carcinoma were found. Descriptive analysis was done for patients’ demographics and clinicopathological features. Kaplan Meier method was used to assess survival outcomes. Results: The incidence of metaplastic breast cancer was 0.5% (31/6180) in our study out of which the most common histopathological differentiation was squamous (45.16%). The second most common was sarcomatoid histology (32.25%), followed by chondroid (9.68%) and mixed histology (12.9%). The median age at diagnosis was 60 years ranging from 28 to 82 years. 64.15% of patients were post-menopausal. At presentation, three (9.67%) patients had metastatic disease while the rest were diagnosed with early (51.61%) and locally advanced cancers (38.72%). Triple negative cancers (ER/PR/Her2 negative) constituted the vast majority with 22 cases (80.6%) while hormone receptor positive (ER/PR positive, Her-2 negative) and Her-2 neu positive (ER/PR negative) made up the rest with three patients (9.67%) each group respectively. The median overall survival was found to be 39 months (95% CI 25.46 - 52.53). Conclusions: After a thorough search in PubMed and Google Scholar, we could not find a larger case series from India with clinical outcomes for metaplastic breast carcinoma. Our results suggest that metaplastic breast carcinoma is a heterogenous disease. Outcomes of metaplastic breast carcinoma are relatively worse when compared with literature for triple negative breast cancer and breast cancer in general. Further biological understanding may offer valuable insights for newer targets and therapeutic approaches to metaplastic breast cancer.
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]
e16269 Background: Combination of Gem+Nab-P is considered as a dose intense regimen which exhibits synergistic cytotoxic activity and equally effective in increasing survival as FOLFIRINOX regimen in pancreatic cancer. However, number of patients who tolerates such dose intense regimen is found to be less in Indian population. The importance of maintaining optimum RDI is well-known however a low RDI may reflect a poor tolerability. Therefore, the present study aimed to identify desired relative dose intensity and explore the potential of baseline NLR as a prognostic biomarker. Methods: A retrospective chart review was performed of 26 patients with a median age of 65.5 years who received this drug combination either as first-line or second-line treatment for pancreatic adenocarcinoma at a single institution. Treatment outcome was measured using overall survival and toxicities were classified according to CTCAE guidelines. The thresholds for RDI of Gem and Nab-P, and baseline NLR cut-off for predicting survival was calculated by constructing ROC curves. Results: Median overall survival was 11.5 months. Median RDI of Gem and Nab-P was found to be 79% (30-94) and 71% (39 –114) respectively. We estimated a RDI cut-off of 67% in Nab-P and 68% in Gem and observed a statistically significant favorable outcome in patients who received Nab-P with RDI > 67% ( p-0.021). No significant relationship of Gem RDI with outcome was observed. Median overall survival was found to be higher in patients with a baseline NLR < 2.35, patients on D1, D8, D15 treatment regimen and those who received Nano particle bound paclitaxel. Complete assessment of study subjects are enlisted in the table. Grade 3 neuropathy, fatigue, and hyponatremia were reported in 2, 5 and 4 patients respectively. Grade 2 skin rashes and neuropathy were seen in 3 patients each. Conclusions: Our study concludes that tolerability of Gem+Nab P is a concern and it is expected to exhibit a durable response only if it achieves an optimum RDI of Nab-P. The study indicates varied efficacy in different pharmaceutical preparations of paclitaxel favoring the use of nano-particle formulations. The study also indicates that baseline NLR is an important prognostic biomarker in pancreatic cancer[Table: see text]
Background: According to the GLOBOCAN 2018 report, the estimated incidence of lung cancer in India was 67,795 in both sexes. The treatment of advanced Non-small cell lung cancer (NSCLC) saw a major paradigm shift with recent advances in molecular-targeted therapy. Immune checkpoint blockade therapy is one such novel strategy with promising clinical benefits in advanced NSCLC. Programmed cell death receptor-1/Programmed cell death ligand-1 (PD-1/PD-L1) pathway is one such checkpoint and has thus become the current area of interest in the treatment of lung carcinoma. The PD-1/ PD-L1 pathway is under active investigation as it represents a promising therapeutic target in NSCLC. The expression of PD-L1 in tumor cells has been suggested as a predictive marker of the clinical response to PD-1/ PD-L1-targeted therapy. Methods: This study was carried out at the Department of Pathology, Health Care Global Specialty Hospital, Bangalore from May 2018 to May 2019. In this study, we analyzed pattern of PD-L1 expression by immunohistochemistry testing using our own Laboratory Developed Test (LDT) in NSCLC patients. Results: Our study group comprised 50 patients of NSCLC. Among our study population, 40% of the patients exhibited PD-L1 immunopositivity (≥1%) with 28% of them having any expression (TPS 1% - 49%) and 12% of them having a high expression (TPS ≥ 50%) of PD-L1. Majority of them exhibited adenocarcinoma type of NSCLC under which the solid subtype showed a direct correlation with PD-L1 positivity (p-value: 0.004) with a poorly differentiated tumor histology being common in our population in relation to PD-L1 positivity (p-value: 0.043). PD-L1 expression did not correlate with age, gender, smoking status or clinical stage in our study. No association was found between tumor histology (SCC or AC) and driver mutation status with expression of PD-L1 in the present study. Conclusions: In our study, PD-L1 immunopositivity was found in 40% of patients and majority of them exhibited adenocarcinoma type of NSCLC. There was no correlation of PD-L1 expresion with age, gender, clinical stage, smoking status and tumor histology.
e16507 Background: Oesophageal cancer is the twelfth most common cancer worldwide and seventh leading cause of cancer related death. Neoadjuvant treatment in addition to surgery has shown improved overall survival compared to surgery alone in resectable oesophageal cancer. We aimed to analyse the survival outcome among locally advanced oesophageal carcinoma patients in neoadjuvant setting. Methods: We analysed 37 patients with locally advanced carcinoma of oesophagus from 2015 to 2019 who underwent neoadjuvant chemoradiotherapy followed by surgical excision of tumour. Descriptive analysis was used for demographic data. overall survival and disease free survival was analysed using Kaplan-Meier survival analysis. Results: Our study includes 20 males (54%) and 17 females (45%). Over all consumption of Tobacco and alcohol consumption was found to be 64% and 18% respectively. The most common tumour site in this study was middle oesophagus (56%) followed by lower (37%) and upper (5%). Histopathologically, moderately differentiated squamous cell carcinoma constituted the highest (62%), followed by well differentiated squamous cell carcinoma (21%) and poorly differentiated carcinoma (16%). The pathological stage post chemoradiotherapy was 80%, 50% and 57% for stage I, II and III respectively. Median over all survival is 60 months and no statistical difference in stage I and stage II. Median over all survival for poorly differentiated squamous cell carcinoma is 16 months and lower one third of squamous cell carcinoma is 37 months. Complete pathological response is 42 %. Conclusions: Our study concluded that patients with tobacco and alcohol consumption have poorer survival. Prognosis was worst for patients with lower end oesophagus and poorly differentiated type. Disease free survival was better for patients who achieved complete pathological response when compared to partial responders.
e15522 Background: Taxanes are an integral part of chemotherapy for a broad range of tumor types. The usual toxicities associated with Taxane use are peripheral neuropathy, myelosuppression and musculoskeletal adverse effects. Very few studies have reported taxane induced pulmonary toxicity objectively. In our study we explored Taxane induced pulmonary toxicity based on discrete CT findings. Methods: 40 non-smokers diagnosed with Her-2 negative breast cancer who received Taxane monotherapy from 2017 to 2018 were retrospectively analyzed for pre and post therapy CT changes. Following CT findings were considered significant as pulmonary toxicity; (a) Nonspecific area with ground-glass attenuation, (b) multifocal areas of airspace consolidation, (c) patchy distribution of ground-glass attenuation accompanied by interlobular septal thickening and (d) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. The CT findings were assessed independently by two radiologists and one pulmonologist. Results: Our study showed that 5 patients (12.5%) developed pulmonary changes on chest CT post Taxane therapy as summarized in Table. Conclusions: Our study shows that taxane has more potential to induce pulmonary toxicity than reported in present literature. Given that taxanes are the most widely used chemotherapy, it is of utmost necessity to be cognizant of this under-reported potentially fatal adverse effect in a large population. Further studies should be conducted to better understand the true potential, mechanisms and patterns of taxanes induced pulmonary toxicity. [Table: see text]
With advances in targeted and personalized treatment for lung cancer, molecular analysis of tumors is routinely performed for sequencing of treatment options in patients with advanced non-small-cell lung cancer (NSCLC). Oncogene addiction due to driver mutations includes EGFR exon 20 insertion mutations, MET amplification, EML4-AL, KRAS G12C point mutations, RET rearrangements, HER2 amplification and mutations, and FGFR amplification and translocations. A re-biopsy at the time of tumor recurrence or progression after first-line treatment failure is important for further molecular assessment and personalized therapy. However, repeat tumor biopsies are fraught with challenges including access to the tumor, sample inadequacy, patient consent, patient performance status, safety, or physician's choice or assessment. Cytological specimens are gaining importance but are limited due to validation difficulties. Liquid biopsies, which are minimally invasive have shown promise to assess dynamic biomarkers using ctDNA analysis and are thus frequently considered in routine clinical practice in advanced NSCLC patients to guide further targeted treatment. Here we present a comprehensive review that emphasizes the significance of performing tumor re-biopsy in advanced stage NSCLC patients following resistance to first-line treatment and simultaneously highlights the current challenges in performing the same and the current status and future perspectives of liquid biopsy in NSCLC.
e18802 Background: SAR, a known adverse event of cancer therapy has variable severity. Despite the availability of many approved grading tools, there is still a lack of a globally applicable grading system. To address this, World Allergy Organization (WAO) created a uniform 5-grade classification system which was modified recently to be applicable for all SAR’s. This study aims to understand the incidence and severity of chemotherapy induced SAR and overall response rate (ORR) of rechallenged drugs in a tertiary cancer center. Methods: A retrospective single centered analysis of 103 patients with chemotherapy induced SAR was carried out. Patients were stratified based on age, gender, drugs given, dose number and severity of reaction. We used Modified WAO Grading System for assessing the severity. Descriptive statistics was applied to decipher the data. ORR is defined as the proportion of patients who have a partial or complete response to rechallenged drugs using RECIST Criteria for solid tumors and Lugano Classification for lymphoma. Results: Among 103 patients who reported SAR, 63.1% were female and 64.1% patients were less than 60 years of age. Among the 22 drugs, median dose number was high for Oxaliplatin (6) and Carboplatin (5). SAR was more observed with Paclitaxel (20.39%), Carboplatin (17.48%) and Rituximab (13.59%). However, carboplatin and rituximab had more incidence of grade 1 SAR(25.92% and 29.63% respectively). Grade 1 SAR (39.80%) were reported the highest followed by grade 3 (29.13%), grade 5 (13.59%), grade 2 (11.65%), and grade 4 (5.83%). Cetuximab precipitated the most grade 5 reactions (33.33%). Among patients exhibiting SAR with Paclitaxel, 42.86% were switched to alternatives, Nab-paclitaxel (28.57%) being preferred the most. Carboplatin was changed to cisplatin in 16.66% patients and Nanosomal docetaxel lipid suspension replaced docetaxel in 42.86% patients who reported SAR with carboplatin and docetaxel respectively. Rituximab was rechallenged the most (11.65%) off which one patient had reaction. ORR was observed to be 62.5% and 50% among rechallenged Paclitaxel and Rituximab respectively. The incidence of SAR is depicted in the below table. Conclusions: The study inferred that most SAR reactions occurred with Paclitaxel and Carboplatin. Oxaliplatin and Carboplatin presented with delayed SAR. Grade 1 and grade 3 reaction were relatively more. Cetuximab reported the most grade 5 reactions. ORR of rechallenged drugs should be monitored in further larger studies.[Table: see text]
Background: Lymphomas are a heterogenous group of lymphoproliferative disorders arising from B-cells, T-cells or Natural Killer (NK) cells, which are classified into Hodgkin and Non-Hodgkin Lymphoma. Hodgkin Lymphoma is categorised into Classical Hodgkin Lymphoma (CHL) and Non Classical types according to clinical, histomorphological, phenotypic and genotypic features. In India, the incidence of lymphoma has increased in the last decade and the increased incidence is found in patients of fifth and sixth decade. The etiology of HL remains unclear, usually arises denovo or seen to arise from Epstein-Barr viral infection. Analyzing expression of abundant EBV small nuclear RNA transcripts (EBER) in RS cells by RNA In Situ Hybridisation (RISH) and immunehistochemical expression of latent membrane protein (LMP1)together are more conclusive for identifying EBV-related Hodgkin Lymphomas than either assay alone. Here we studied etiopathogenic role of EBV in HL.
Methods: This was a hospital based ethics approved study conducted at the Department of Pathology, Health Care Global Specialty Hospital, Bangalore from June 2017 to May 2019.
Results: We found among 57 cases of Hodgkin Lymphoma, 33 were EBER positive, 37 were LMP 1 positive, overall, 41 cases (71.9%) were EBV positive. There was statistically significant association between gender and LMP1 (p=0.037). There was a statistically significant association of EBER with morphological subtypes (p=0.034) and Ann Arbor Staging (p=0.013). EBER expression was more frequently found in mixed cellularity subtype and in advanced stages of Hodgkin Lymphoma.
Conclusion: EBER expression had significant association (p=0.034) with HL subtypes and EBV also had significant association (p=0.041). But, withLMP1 expression alone, there was no significant association (p=0.191) with the subtypes, suggesting analysing expression of both EBER and LMP1 for studying association of EBV in HL.
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