Biomarker testing in lung cancer: from bench to bedside.

Non-small-cell lung cancer (NSCLC) is the poster child of personalized medicine. With increased knowledge about biomarkers and the consequent improvement in survival rates, NSCLC has changed from being a therapeutic nihilistic disease to that characterized by therapeutic enthusiasm. The routine biomarkers tested in NSCLC are EGFR, ALK, and ROS1.

Uniqueness of lung cancer in Southeast Asia.

Lung cancer varies between Caucasians and Asians. There have been differences recorded in the epidemiology, genomics, standard therapies and outcomes, with variations according to the geography and ethnicity which affect the decision for optimal treatment of the patients. To better understand the profile of lung cancer in Southeast Asia, with a focus on India, we have comprehensively reviewed the available data, and discuss the challenges and the way forward.

: A Novel ROS1 Oncogenic Fusion Detected on Next Generation Sequencing.

Advanced Non-Small Cell Lung Carcinoma (NSCLC) patients with gene rearrangement have shown significant therapeutic responses to tyrosine kinase inhibitors approved by the US Food and Drug Administration, with approximately 40 fusion partners documented in the existing literature. Our report highlights a novel fusion partner of that has demonstrated a conclusive response to the current standard of treatment.

AI-based pipeline for early screening of lung cancer: integrating radiology, clinical, and genomics data.

Background: The prognosis of lung carcinoma has changed since the discovery of molecular targets and their specific drugs. Somatic Epidermal Growth Factor Receptor () mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. However, in a resource-constrained country like India, panel-based next-generation sequencing cannot be made available to the population at large.

COVID-19 and Cancer: A Comparison of the Two Important Pandemic Waves in an Indian Cancer Patients' Cohort.

Ullas BatraIt is well known that patients with cancer are at an increased risk of severe COVID-19. There are no reports that depict the differences in outcomes in cancer patients between the two waves of the pandemic. This is a real-world experience aimed at characterizing the differences in demographics, clinical features, treatment details, and outcomes in COVID-19-positive cancer patients between the two pandemic waves.

Extradural spinal melanoma: is it primary or metastatic? A case report with a brief review of literature.

Melanocytic lesions involving the central nervous system are extremely rare and pose a diagnostic challenge owing melanoma being the third most common malignancy metastasizing to the spine. Morphology and immunohistochemistry are identical in both primary and secondary cases, and hence may not help in rendering a final diagnosis. Molecular alterations involving melanomas of the spine and melanomas elsewhere are distinct and help establish the appropriate diagnosis.

A novel EML4-NTRK3 fusion in lung adenocarcinoma with dramatic response to entrectinib.

In-frame fusions in NTRK genes, with intact kinase domain, have been reported to occur at higher frequencies in rare tumors like infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinoma, whereas they occur at very low frequencies in common malignancies like NSCLC and colon cancers (0.1%-1%). Despite the rare occurrence, these alterations have gained importance owing to approval of drugs like entrectinib and larotrectinib targeting the kinase domain of the gene.

Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort.

Objective: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S).

Methods: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans.

KRAS mutated Non-Small Lung Carcinoma: A Real World Context from the Indian subcontinent.

Background: KRAS, although a common variant of occurrence (~20% of non-small-cell lung carcinoma [NSCLC]) has been untargetable, owing to the molecular structure which inherently prevents drug binding. KRAS mutations in NSCLC are associated with distinct clinical profiles including smokers and mucinous histology. KRAS G12C mutations account for ~40% KRAS altered NSCLC, but NSCLC being a geographically diverse disease, the features may be distinct in this part of the world.

Immunotherapy in advanced non-small-cell lung cancer (NSCLC) after progression on chemotherapy: real-world results from a prospective institutional cohort.

To analyze the outcomes of patients receiving immunotherapy (IO) with advanced non-driver mutated non-small-cell lung cancer (NSCLC) after progression on systemic treatment. The overall survival (OS), progression-free survival (PFS) and best response to IO of 64 patients who met our inclusion criteria were analyzed. Median follow-up, OS and PFS were 35.

Founder BRCA1 mutations in Nepalese population.

Background: Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people.

Methods: Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021.

All EGFR mutations are (not) created equal: focus on uncommon EGFR mutations.

Purpose: Most common EGFR mutations in NSCLC include del19 and exon 21 L858R. Approximately 10% of patients have uncommon EGFR mutations (indels, missense mutations involving G719, L861 and S768 codons, and exon 20 insertions) that do not respond to TKIs.

Methods: Of 490 EGFR mutated NSCLC samples, 60 cases harboring uncommon/compound EGFR mutations were reviewed retrospectively, and 44 were included for survival analysis.

Machine learning-based algorithm demonstrates differences in del19 and L858R EGFR subgroups in non-small cell lung cancer: a single center experience.

Background: Exon del19 and L858R mutations account for 90% of EGFR mutant non-small cell lung cancer (NSCLC). LUX lung 3 and 6 initially reported a survival difference between these two. However, other studies did not demonstrate the same.

Unusual Resistance Mechanisms in a Case of -Rearranged NSCLC: A Case Report.

The unprecedented growth of the high-throughput next-generation sequencing has facilitated the identification of rare oncogene fusions such as for NSCLC. rearrangement has been observed in only 2% of cases of NSCLC and has been successfully targeted using various tyrosine kinase inhibitors including crizotinib. However, the on-target and off-target mechanisms of the resistance are still vague.

Clinicopathological aspects of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutated non-small cell lung carcinoma in an Indian cohort: is there a difference?

Introduction: Activating mutations in the BRAF gene have been reported in 0.8%-8% cases of NSCLC. Traditionally, diagnostics have mainly focused on detection of V600E and modalities like mutation specific IHC, allele specific real-time PCR have been utilized.

EGFR detection by liquid biopsy: ripe for clinical usage.

With the International Association for the Study of Lung Cancer (IASLC) recommendations promoting liquid biopsy as a primary detection tool, a new era of research has begun. The authors aimed to study the concordance of plasma genotyping platforms against the tissue gold standard. 184 patients with non-small cell lung cancer underwent EGFR genotyping using Cobas, droplet digital polymerase chain reaction (ddPCR) and Therascreen assays from 2019-2020.

Robust home brew fragment sizing assay for detection of MET exon 14 skipping mutation in non-small cell lung cancer patients in resource constrained community hospitals.

Background: A mutation/deletion involving donor or acceptor sites for exon 14 results in splicing out of exon 14 of the mesenchymal epithelial transition (MET) gene and is known as "MET exon 14 skipping" (ΔMET14). The two recent approvals with substantial objective responses and improved progression-free survival to MET inhibitors namely capmatinib and tepotinib necessitate the identification of this alteration upfront. We herein describe our experience of ΔMET14 detection by an mRNA-based assay using polymerase chain reaction followed by fragment sizing.

Mutational landscape of Juvenile Myelomonocytic Leukemia (JMML)-A real-world context.

Introduction: Juvenile myelomonocytic leukemia (JMML) is a rare childhood neoplasm (<5% cases), which has been categorized under myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the recent classification by the World Health Organization.

Methods: We developed a 51-gene (151.5kB) low-cost targeted myeloid panel based on single-molecule molecular inversion probes to comprehensively evaluate the genomic profile of Juvenile myelomonocytic leukemia (JMML).

Are all ALK variants created equal? Clinicopathologic features and outcomes: a propensity-matched study.

Anaplastic lymphoma kinase (ALK) rearranged NSCLC comprises a molecularly distinct subgroup occurring in 10% cases. Various EML4-ALK and non EML4 variants are known to occur which can be detected only on NGS and show differential TKI responses. 113 ALK-IHC positive cases were subjected to a custom panel-based NGS for detection of ALK variants.

IHC versus FISH versus NGS to detect ALK gene rearrangement in NSCLC: all questions answered?

Aims: Anaplastic lymphoma kinase () rearranged non-small cell lung carcinoma (NSCLC) is a distinct molecular subtype and rapid approval of tyrosine kinase inhibitors (TKIs) has necessitated rapid and sensitive diagnostic modalities for the detection of this alteration. Gene rearrangements can be identified using many techniques including fluorescence in situ hybridisation (FISH), reverse transcriptase-PCR, next-generation sequencing (NGS) and immunohistochemistry (IHC) for fusion oncoprotein expression. We aimed to determine the concordance between IHC, FISH and NGS for biomarker detection, and determine differences in sensitivity, and survival outcomes.

Malfeasance of KRAS mutations in carcinogenesis.

Activating mutations in the KRAS gene (Kirsten rat sarcoma 2 viral oncogene homolog gene) are commonly seen across the various solid organ and hematolymphoid neoplasms. With the likelihood of the mutation specific KRAS inhibitor entering clinical practice, the present studies profiled the landscape of these mutations in the Indian population to add to databases and posit the clinical utility of its emerging inhibitors. This study included 489 formalin fixed paraffin-embedded (FFPE) tissue samples from consecutive patients during a 5-year period (2015-2019).

EGFR and PDL1: A Match (Not) Made in Heaven-A Real-World Retrospective Analysis of PDL1 Expression in EGFR-Mutated NSCLC.

Introduction: EGFR (epidermal growth factor receptor) mutant NSCLC (non-small cell lung carcinoma) comprises 35-40% of cases in the Asian NSCLC cohort, compared to 15-20% in the rest of the world. Improved response rates have been observed in terms of PFS (progression-free survival) and ORR (overall response rate) when treated with EGFR TKIs (tyrosine kinase inhibitors). However, resistance eventually ensues regardless of the generation of TKI used.