Uniqueness of lung cancer in Southeast Asia

The Lancet Regional Health - Southeast Asia, Journal Year: 2024, Volume and Issue: 27, P. 100430 - 100430

Published: July 8, 2024

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

Language: Английский

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Gefitinib vs Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Variant Lung Cancer—Long-Term Results of a Randomized Clinical Trial

JAMA Oncology, Journal Year: 2024, Volume and Issue: 10(6), P. 824 - 824

Published: April 25, 2024

This randomized clinical trial examines whether adding chemotherapy with pemetrexed and carboplatin to gefitinib improves survival among patients epidermal growth factor receptor ( EGFR )–variant non–small cell lung cancer.

Language: Английский

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PD-1/PD-L1 blockade therapy with atezolizumab: a new paradigm in the treatment of non-small cell lung cancer (NSCLC)

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 26, 2025

Language: Английский

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Targeting exon mutations in NSCLC: clinical insights into LAG-3, TIM-3 pathways, and advances in fourth-generation EGFR-TKIs

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(6)

Published: May 5, 2025

Language: Английский

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Molecular analysis for EGFR, ALK, and ROS1 alterations in over 3000 Indian patients with non-small-cell lung cancer: A retrospective observational study

Cancer Research Statistics and Treatment, Journal Year: 2024, Volume and Issue: 7(1), P. 11 - 18

Published: Jan. 1, 2024

Background: Accurate molecular testing in non-small-cell lung cancer (NSCLC) is of paramount importance for treatment, prediction, and prognostication. Objectives: We aimed to comprehensively describe the clinicopathological profile Indian patients with NSCLC regard alterations epidermal growth factor receptor ( EGFR), anaplastic lymphoma kinase ALK), c-ros oncogene 1 ROS1 ). Materials Methods: conducted a retrospective analysis tissue samples tested between January 2015 December 2021 at Metropolis Healthcare Limited global referral laboratory facility Mumbai, Maharashtra, India. Testing was EGFR by real time reverse transcriptase polymerase chain reaction (RT-PCR) Sanger sequencing , ALK immunohistochemistry (IHC), fluorescence situ hybridization (FISH), (ROS1) FISH. analyzed positivity status determined trends results targets cases. Results: Out 3220 malignancy, 1750 (54.3%) were out which 510 (29.1%) positive. The most common mutation detected exon 19 (334/510, 65.5%), followed 21 (164/510, 32.2%). A total 1548 (48.1%) cases IHC, 125/1548 (8.1%) showed positivity, while among 372/3220 (11.6%) FISH, 29/372 (7.8%) In squamous cell carcinoma, rate IHC 5.3%. Of 372 353 (94.9%) as well; 98.9% concordance observed positive 370/3220 (11.5%) low 13/370 (3.5%). Conclusions: have 29% 8.1% 3.5% when RT-PCR, respectively. detailed using next-generation (NGS) may help detect higher number amenable therapy.

Language: Английский

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Profile of patients with lung cancer at a tertiary care hospital in Nepal: A retrospective analysis

Cancer Research Statistics and Treatment, Journal Year: 2024, Volume and Issue: 7(4), P. 396 - 402

Published: Oct. 1, 2024

ABSTRACT Background: Cases of lung cancer are increasing in Nepal. Identifying histological types can influence prognosis and survival rates different cancer. Objectives: The primary objective this retrospective study was to provide a comprehensive clinical profile patients with secondary analyze the demographic characteristics these patients. Materials Methods: We analyzed data for 192 diagnosed at Purbanchal Cancer Hospital, Birtamode, Nepal registered between January 2020 December 2023. categorized cases into three categories: non-small-cell (NSCLC), small-cell cancer, others/not defined. NSCLC further classified squamous cell carcinoma adenocarcinoma. A univariate analysis outlined patient attributes, classifications, stage treatment received, while bivariate assessed associations using Chi-square tests. Results: included study. Of them, 145 (75.5%) had NSCLC, adenocarcinoma being most prevalent subtypes. Around 97% (186 patients) were an advanced stage. Only one-third (62 patients, 32.3%) reported history smoking, 90% (173 over 50 years old. Additionally, one fourth (43 22.4%) hypertension. Chemotherapy radiation therapy used treatments. Conclusion: is common type, higher proportion non-smokers. This emphasizes need investigations risk factors. Early detection tailored interventions critical reducing burden

Language: Английский

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Amivantamab: A narrative drug review

Cancer Research Statistics and Treatment, Journal Year: 2023, Volume and Issue: 6(2), P. 261 - 271

Published: April 1, 2023

ABSTRACT Epidermal growth factor receptor ( EGFR ) activating mutations are known oncogenic drivers in non-small-cell lung cancer (NSCLC), with 85% attributable to an exon 19 deletion or 21 L858R point substitution. The next most common is 20 insertion mutation (Ex20Ins), which results altered active site that sterically interferes tyrosine kinase inhibitor (TKI) binding, resulting a poorer response rate TKIs. Amivantamab (JNJ-61186372), fully humanized EGFR- mesenchymal-epithelial transition (MET) bispecific antibody has been approved for use adults locally advanced metastatic NSCLC Ex20Ins mutations, whose disease progressed on after platinum-based chemotherapy. To prepare this review, we searched various websites, including the European Medicines Agency Drug Manual, United States Food and Administration, PubMed, Science Direct, UpToDate using search terms, “Amivantamab,” “NJ-61186372,” “amivantamab-vmjw,” and” “ exon20ins.” We shortlisted 121 articles published between 2015 2023, of 49 were included. This review discusses clinical indications, adverse effects, safety, pharmacodynamics, pharmacokinetics, key research trials investigated amivantamab.

Language: Английский

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Identification of a rare EGFR exon 18 mutation in lung adenocarcinoma using targeted next-generation sequencing as a tool for precision medicine

Cancer Research Statistics and Treatment, Journal Year: 2023, Volume and Issue: 6(4), P. 589 - 592

Published: Oct. 1, 2023

CASE SUMMARY History and examination A 63-year-old female patient presented to the Tata Memorial Hospital, a tertiary cancer hospital in Mumbai, India, May 2023 with 3-month history of right-sided upper backache right neck swelling. She was known be hypertensive, had hypothyroidism, on medications for these illnesses. no other comorbidities, addictions, or family cancer. Her Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1. Investigations diagnosis The initially been evaluated by her primary care physician complaints undergone fine needle aspiration cytology (FNAC) supraclavicular lymph node March 2023, which revealed metastatic carcinoma. contrast-enhanced computerized tomography (CECT) thorax performed April 2 × cm2 nodular lesion medial basal segment lower lobe lung [Figure 1a]. then referred our further workup management. biopsy performed, thyroid transcription factor 1 (TTF1) positive adenocarcinoma. This specimen sent next-generation sequencing (NGS). Positron emission (PET) June 1.9 2.4 1.7 cm3 mass (maximum standardized uptake value [SUVmax], 11.67) necrotic mediastinal nodes, frontal brain perilesional edema. Contrast-enhanced magnetic resonance imaging (MRI) heterogeneously enhancing grey-white matter junction measuring 1.6 1.5 cm2, disproportionate edema suggestive metastasis 1b]. planned systemic therapy palliative intent, while awaiting NGS report.Figure 1: (a) computed showing soft tissue (marked black arrow) abutting adjacent costal diaphragmatic pleura (b) (CE) an altered signal intensity metastasisNext-generation excerpts from discussion molecular tumor board Molecular testing in-house using amplicon-based baseline formalin-fixed paraffin-embedded (FFPE) tissue. gene panel covers hot spots 50 genes 3159 unique variants, including single nucleotide variants (SNVs), indels (insertions deletions), fusions, copy-number variations (CNV). It includes automated library template preparation followed at average depth ~4000X. mutation epidermal growth receptor (EGFR) exon 18 p.E709_T710delinsD, variant allele frequency (VAF) 12.92% [Table 1]. rare EGFR deletion-insertion discussed board, recommendation made EGFR-targeted (gefitinib) combination chemotherapy (pemetrexed + carboplatin). based earlier study Noronha et al.[1] As asymptomatic metastasis, radiation oncology team decided keep under observation. also recommended considering osimertinib. However, could not afford medicine, therefore, do time progression consider osimertinib, results progression.Table Next-generation report done 2023DISCUSSION Introduction belongs erythroblastic leukemia viral oncogene homolog (ERBB) tyrosine kinases is alternatively as ERBB1/human (HER1), located chromosome 7 human genome. transmembrane glycoprotein extracellular ligand-binding domain intracellular kinase domain, primarily regulates signaling pathways control cellular proliferation.[2] pathway critical that various processes, cell growth, proliferation, differentiation, survival, migration 2].[2,3] activated binding ligands, such (EGF), transforming alpha (TGF-α), others, surface. ligand (such EGF) leads dimerization induces conformational change, activation downstream pathway. Further, this its domain. phosphorylates specific residues cytoplasmic activates signaling. Next, autophosphorylates tail. These phosphorylated serve docking sites molecules. Phosphorylated recruit adaptor proteins receptor-bound protein (Grb2) through their Src Homology (SH2) domains. Grb2, turn, recruits Son Sevenless (SOS) protein. complex, composed Grb2 SOS, facilitates small guanosine triphosphatase (GTPase) protein, Ras. SOS promotes conversion Ras inactive GDP-bound state active GTP-bound state. Active Ras-GTP initiates cascade events. Activated triggers series activations mitogen-activated (MAPK) ultimately phosphorylation signal-regulated (ERK). ERK translocates nucleus factors, leading changes expression. can promote stimulates phosphoinositide 3-kinase (PI3K) serine-threonine Akt, metabolism.[2,4] complex interconnected networks. Dysregulation pathway, often due mutations overexpression related proteins, implicated cancers, making it important target therapy.[4]Figure 2: Epidermal figure has adapted Brambilla al. EGF = factor, receptor, Akt Serine-threonine kinase, PI3K Phosphoinositide 3-kinase, Growth 2, Sevenless, RAS Rat sarcoma, RAF Rapidly accelerated fibrosarcoma, MEK Mitogen regulator MAPK Mitogen-activated kinaseEGFR established well-established cancer.[5] functional plays crucial role development non-small-cell (NSCLC). Several types have identified NSCLC, two most common being 19 deletion L858R point 21 2].[2,6]EGFR comprises region deoxyribonucleic acid (DNA) gene. constitutively active. Similarly, constitutive are more commonly found non-smokers light smokers prevalent patients Asian descent.[5] They majorly associated NSCLC adenocarcinoma histology. Patients EGFR-mutated respond well targeted inhibitors (TKI), gefitinib, erlotinib, afatinib.[2] drugs specifically mutated inhibit aberrant signaling, shrinkage improved oncologic outcomes. discovery led significant shift treatment landscape, highlighting importance profiling guiding decisions NSCLC.[7-9]Table frequencies different mutations. data were Harrison al.EGFR therapeutics Lung widely characterized activating driver across population, include exons 18, 19, 21. frequently observed p.E746_A750 variant, p.L858R p.G719X 18.[10] Among these, classical account ~90% all mutations.[9,10] Besides mutations, occurrence reported.[6] In present study, we case NGS-based diagnosis. frequent (75.6% mutations) p.E709X (15.9%) adenocarcinoma.[11,12] Here, p.E709_T710delinsD; previously reported only few studies, Chinese 3.6% (3/82) frequency, ~0.25% (18/6942) Caucasian population per available cBioPortal.[11,13] Interestingly, able identify four individual studies type (E709_T710delinsD) so far.[14-17] non-canonical uncommon shown variable outcomes single-agent TKI chemotherapy.[18] Xu al., 3/82 (3.6%) treated first-generation (1G) (1/3), second-generation (2G) (1/3) (1/3). authors progression-free survival (PFS) median 11.1 months 1G compared (median, 7.7 months) 5 18. similar PFS 2G (afatinib) 18.[12] Another showed good erlotinib.[14] addition, deletions sensitive afatinib.[15-17] summary, suggests (p.E709_T710delinsD) but potentially targetable responsive NSCLC. Our advised pemetrexed carboplatin gefitinib (chemotherapy TKI), study. CONCLUSION describes identification sample. provided opportunity scrutinize mutation. technology enables us plan variant-specific disease Financial support sponsorship Nil. Conflicts interest Vanita Noronha, Anuradha Choughule, Kumar Prabhash members editorial Cancer Research, Statistics, Treatment. such, they may access information and/or participated perceived influencing publication manuscript. recused themselves peer review, editorial, decision-making process manuscript, ensure content objective unbiased.

Language: Английский

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Real but rare: Lessons from a case of lung adenocarcinoma with an uncommon EGFR exon 18 alteration

Cancer Research Statistics and Treatment, Journal Year: 2024, Volume and Issue: 7(1), P. 141 - 142

Published: Jan. 1, 2024

Profiling of solid tumors using next-generation sequencing is a robust tool to detect both common and uncommon genetic variants that influence patient management.[1] The molecular tumor board article by Jha et al.,[2] published in the last issue journal, was an interesting example multigene testing-directed therapeutic decision-making strategy. A rare EGFR exon 18 insertion-deletion (indel) mutation, p.E709_T710delinsD, detected at baseline. Gefitinib started, combination with chemotherapy, after discussion board, as could not afford third-generation tyrosine kinase inhibitor (TKI), osimertinib.[2] most commonly reported mutation G719X position, which accounts for 1.5-3% all alterations.[3,4] Of these, almost 41% occur compound mutations.[4,5]EGFR mutations E709 position are either indels, noted present case or point (E709X), comprising meager 1.5% reported. Among indel usually stand-alone alteration, while E709X seen other driver alterations. presence influences response TKI.[6] In case, this crucial picked up targeted panel performed on baseline biopsy tissue. This would have been missed single gene real-time polymerase chain reaction testing commercially developed kits do include primers mutation.[7] addition, since extremely rare, alteration relatively low variant allelic frequency 12.9%, orthogonal test different platform should confirmation. Preclinical studies Kobayashi al.[8] Bs/F3 NIH/3T3 cell lines retrovirally transduced G719X, E709K, delE709_T710insD mutations, showed inhibition afatinib resistance gefitinib, erlotinib, even osimertinib. However, LUX-Lung trials, led United States-Food Drug Administration approval treatment S768I, L861Q did show comparable benefit along dose-limiting toxicity.[3] study Xu al.[6] 82 patients non-small-cell lung cancer harboring alterations median progression-free survival (mPFS) 7.7 months (95% CI, 4.2-11.2) who were treated first-generation TKIs. better mPFS second-generation TKI, 11.3 5.6-17.1) those received TKI chemotherapy 11.1 5.9-16.4). Rare like p.E709_T710delinsD be enable pooling data from substantial number patients, help formulate evidence-based decisions. Like pooled trials enabled such reports, subsequent usher new precision "AURA" these Financial support sponsorship Nil. Conflicts interest There no conflicts interest.

Language: Английский

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Homologous recombinant repair gene mutations across tumors

Cancer Research Statistics and Treatment, Journal Year: 2024, Volume and Issue: 7(1), P. 131 - 132

Published: Jan. 1, 2024

We read with great interest the article titled, "Pan-cancer analysis of spectrum homologous recombination DNA repair (HRR) pathway genes in Indian population: A retrospective observational study," published last issue journal.[1] In their study, Parween et al.[1] described frequencies recombinant gene mutations across various tumor types an cohort. They selected a subset patients at least one mutation 15 HRR genes, including BRCA1, BRCA2, and ATM. relates to cell mechanisms that prevent replication when have occurred. Numerous different responsible for increase risk cancer but also predict clinical response platinum-based chemotherapy new therapeutic agents (poly [ADP-ribose] polymerase inhibitors [PARPi]), through synthetic lethality.[2] Clinical efficacy has largely been investigated gynecological cancers (ovarian breast), prostate, pancreatic cancers, scarce data studied its use other types. provided thorough overview prevalence total HRR, stratifying according site. Interestingly, percentages identified seemed unusually high among population comparison studies.[2] The authors mentioned discrepancy between results numbers Caucasian population.[3] However, it should be noted were derived from already having mutation, as this was inclusion criterion. could draw parallel EGFR mutations, which are much more prevalent Asian population.[4,5] While latter may correlated air pollution, evidence is less robust mutations.[6] ethnic differences thought originate environmental factors transmitted hereditarily.[7] Specific primary origin critical PARPi efficacy. For instance, prostate cancer, most benefits reported PROfound trial driven by ATM mutations.[8] POLO trial, olaparib maintenance metastatic no overall survival benefit observed, questioning relevance giving toxic drug poor prognostic setting.[9] Finally, even ovarian where demonstrated impressive benefits,[10,11] long-term suggested decrement late treatment lines, leading multiple withdrawals. To conclude, interesting insights into frequency population. question whether would yield those populations answered prospectively, considering importance type Financial support sponsorship Nil. Conflicts There conflicts interest.

Language: Английский

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