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Article ; Online: Is There a Unicorn Among the Uncommon EGFR Mutations?

Tan, Wan Ling / Lim, Darren Wan-Teck

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2023 Volume 18, Issue 2, Page(s) 129–132

MeSH term(s)	Humans ; Lung Neoplasms/genetics ; Carcinoma, Non-Small-Cell Lung/genetics ; Mutation ; ErbB Receptors/genetics ; Protein Kinase Inhibitors
Chemical Substances	ErbB Receptors (EC 2.7.10.1) ; Protein Kinase Inhibitors ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Editorial
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2022.11.009
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Article: Targeting the metastatic niche through anti-angiogenic approaches in epidermal growth factor receptor mutant non-small cell lung cancer.

Tan, Wan Ling / Tan, Daniel S W

Translational lung cancer research

2018 Volume 7, Issue Suppl 1, Page(s) S13–S18

Language	English
Publishing date	2018-02-16
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.21037/tlcr.2017.11.12
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Article: The continuing role of epidermal growth factor receptor tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung.

Tan, Wan Ling / Ng, Quan-Sing

Translational lung cancer research

2014 Volume 5, Issue 1, Page(s) 106–109

Abstract: Squamous cell carcinoma (SCC) of the lung represents about 20-30% of non-small cell lung cancers (NSCLC) and is associated with a poorer prognosis with limited treatment options. Erlotinib is an approved, standard second-line therapy in this setting, ... ...

Abstract	Squamous cell carcinoma (SCC) of the lung represents about 20-30% of non-small cell lung cancers (NSCLC) and is associated with a poorer prognosis with limited treatment options. Erlotinib is an approved, standard second-line therapy in this setting, besides docetaxel. The LUX-Lung 8 study has shown superior overall survival (OS), progression-free survival (PFS), as well as disease control rates for treatment with afatinib compared to erlotinib in this head-to-head trial in patients with previously treated advanced SCC of the lung, with manageable side effect profile. This is the first and largest prospective phase III trial comparing two different tyrosine kinase inhibitors in patients with advanced SCC of the lung. Whether the results would be practice-changing remains to be seen, especially with the advent of novel immunotherapeutic agents such as nivolumab, which is recently approved for advanced lung SCC.
Language	English
Publishing date	2014-10-11
Publishing country	China
Document type	Journal Article
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.3978/j.issn.2218-6751.2015.10.12
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Article ; Online: Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure.

Saw, Stephanie P L / Tan, Gek San / Tan, Wei Chong / Tan, Aaron C / Lai, Gillianne G Y / Lim, Darren W T / Kanesvaran, Ravindran / Tan, Wan Ling / Tan, Sze Huey / Lim, Kiat Hon / Skanderup, Anders J / Tan, Daniel S W

JTO clinical and research reports

2023 Volume 4, Issue 12, Page(s) 100599

Abstract: Introduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations.: Methods: Patients with treatment-naive advanced EGFR- ... ...

Abstract	Introduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations. Methods: Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine kinase inhibitors (TKIs) were included. pEGFR were measured at baseline and first response assessment using ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time-to-treatment failure (TTF). In exploratory analysis, corresponding change in carcinoembryonic antigen (CEA) levels was evaluated. Results: Between January 1, 2020, and December 31, 2021, 27 patients were recruited. Ex19del comprised 74% (20 of 27) and L858R 26% (seven of 27). Osimertinib was used in 59% (16 of 27), dacomitinib 4% (one of 27), and gefitinib/erlotinib 37% (10 of 27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19 of 27) and 78% (21 of 27), respectively ( Conclusions: Plasma NGS trended toward higher sensitivity than ddPCR in detecting pEGFR, although both had similar concordance in detecting pEGFR clearance. Our results support using NGS at diagnosis and interchangeability of NGS and ddPCR for monitoring, whereas CEA could be explored as a surrogate for pEGFR clearance.
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Journal Article
ISSN	2666-3643
ISSN (online)	2666-3643
DOI	10.1016/j.jtocrr.2023.100599
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Article ; Online: Oncogene-driven non-small cell lung cancers in patients with a history of smoking lack smoking-induced mutations.

Cancer research

2024

Abstract: Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" ( ... ...

Abstract	Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and non-smokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC datasets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to regulation of the cell cycle. These findings suggest that, while the genomic landscape is similar between NSRO-driven NSCLC in smokers and non-smokers, smoking still affects the tumor phenotype independently of genomic alterations.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-23-2551
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Article: Real world efficacy of osimertinib in second line/beyond in patients with metastatic EGFR+ non-small cell lung cancer and role of paired tumour-plasma T790M testing at tyrosine kinase inhibitor resistance.

Ma, Jun / Tan, Sze Huey / Yin, Daniel Xing Cheng / Tran, Nguyen Tuan Anh / Tan, Gek San / Lai, Gillianne Geet Yi / Ang, Mei-Kim / Kanesvaran, Ravindran / Jain, Amit / Rajasekaran, Tanujaa / Tan, Eng-Huat / Lim, Tony Kiat Hon / Tan, Daniel Shao-Weng / Lim, Darren Wan-Teck / Ng, Quan Sing / Tan, Wan Ling

Translational lung cancer research

2023 Volume 12, Issue 4, Page(s) 742–753

Abstract: Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the second/subsequent line after resistance to first- and ... ...

Abstract	Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the second/subsequent line after resistance to first- and second-generation (1/2G) EGFR-TKI. Methods: We reviewed electronic records of 202 patients who received osimertinib from July 2015 to January 2019 in the second/subsequent line after progression on prior EGFR-TKI. Of these, complete data from 193 patients were available. Clinical data including patient characteristics, primary EGFR mutation, T790M mutation status, presence of baseline brain metastases (BM), first-line EGFR-TKI use, and survival outcomes were extracted, and results retrospectively analyzed. Results: Of 193 evaluable patients, 151 (78.2%) were T790M+ (T790M positive) with 96 (49.2%) tissue confirmed; 52% of patients received osimertinib in the second line setting. After median follow up of 37 months, median progression-free survival (PFS) of the entire cohort was 10.3 [95% confidence interval (CI): 8.64-11.50] months and median overall survival (OS) was 20 (95% CI: 15.61-23.13) months. Overall response rate (ORR) to osimertinib was 43% (95% CI: 35.9-50.3%); 48.3% in T790M+ Conclusions: This cohort demonstrated the efficacy of osimertinib in second line/beyond for EGFR+ (EGFR mutation-positive) non-small cell lung cancer (NSCLC). Tissue T790M result appeared more predictive of osimertinib efficacy compared to plasma, highlighting potential T790M heterogeneity and the advantage with paired tumor-plasma T790M testing at TKI resistance. T790M- disease at resistance remains an unmet treatment need.
Language	English
Publishing date	2023-03-15
Publishing country	China
Document type	Journal Article
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.21037/tlcr-22-661
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Article: Multispectral raster-scanning optoacoustic mesoscopy differentiate lesional from non-lesional atopic dermatitis skin using structural and functional imaging markers.

Li, Xiuting / Moothanchery, Mohesh / Kwa, Cheng Yi / Tan, Wan Ling / Yew, Yik Weng / Thng, Steven Tien Guan / Dinish, U S / Attia, Amalina Binte Ebrahim / Olivo, Malini

Photoacoustics

2022 Volume 28, Page(s) 100399

Abstract: Atopic dermatitis (AD) is a chronic and pruritic skin inflammatory disease causing a significant burden to health care management and patient's quality of life. Seemingly healthy skin or non-lesional sites on AD patients still presents skin barrier ... ...

Abstract	Atopic dermatitis (AD) is a chronic and pruritic skin inflammatory disease causing a significant burden to health care management and patient's quality of life. Seemingly healthy skin or non-lesional sites on AD patients still presents skin barrier defects and immune response, which can develop to AD at a later stage. To investigate further the balance between the epidermal barrier impairment and intrinsic immune dysregulation in AD, we exploited multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) to image lesional and non-lesional skin areas on AD patients of different severities non-invasively to elucidate their structural features and functional information. Herein, we demonstrate the objective assessment of AD severity using relative changes in oxygen saturation (δsO
Language	English
Publishing date	2022-08-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2716706-9
ISSN	2213-5979
ISSN	2213-5979
DOI	10.1016/j.pacs.2022.100399
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Article ; Online: Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma.

Nature communications

2023 Volume 14, Issue 1, Page(s) 2781

Abstract: Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with ... ...

Abstract	Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC.
MeSH term(s)	Humans ; Nasopharyngeal Carcinoma/pathology ; Herpesvirus 4, Human/genetics ; Programmed Cell Death 1 Receptor ; CTLA-4 Antigen ; Epstein-Barr Virus Infections ; Neoplasm Recurrence, Local/drug therapy ; Treatment Outcome ; Nasopharyngeal Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols
Chemical Substances	Programmed Cell Death 1 Receptor ; CTLA-4 Antigen
Language	English
Publishing date	2023-05-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38407-7
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Article ; Online: Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

Tan, Aaron C / Lai, Gillianne G Y / Saw, Stephanie P L / Chua, Kevin L M / Takano, Angela / Ong, Boon-Hean / Koh, Tina P T / Jain, Amit / Tan, Wan Ling / Ng, Quan Sing / Kanesvaran, Ravindran / Rajasekaran, Tanujaa / Kalashnikova, Ekaterina / Renner, Derrick / Sudhaman, Sumedha / Malhotra, Meenakshi / Sethi, Himanshu / Liu, Minetta C / Aleshin, Alexey /

Lim, Wan-Teck / Tan, Eng-Huat / Skanderup, Anders J / Ang, Mei-Kim / Tan, Daniel S W

Cancer

2024 Volume 130, Issue 10, Page(s) 1758–1765

Abstract: Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to ...

Abstract	Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. Methods: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples. Results: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). Conclusions: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.
MeSH term(s)	Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/blood ; Lung Neoplasms/pathology ; Male ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Female ; Middle Aged ; Aged ; Retrospective Studies ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/diagnosis ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/blood ; Carcinoma, Non-Small-Cell Lung/pathology ; High-Throughput Nucleotide Sequencing/methods ; Neoplasm, Residual/genetics ; Neoplasm, Residual/diagnosis ; Neoplasm Staging ; Early Detection of Cancer/methods ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/blood ; Adult ; Aged, 80 and over ; Multiplex Polymerase Chain Reaction/methods
Chemical Substances	Circulating Tumor DNA ; Biomarkers, Tumor
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35263
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Article ; Online: Comparison of hepatocellular carcinoma in Eastern versus Western populations.

Choo, Su Pin / Tan, Wan Ling / Goh, Brian K P / Tai, Wai Meng / Zhu, Andrew X

Cancer

2016 Volume 122, Issue 22, Page(s) 3430–3446

Abstract: Hepatocellular carcinoma (HCC) is a heterogeneous disease that remains highly prevalent in many Asian countries and is the second most common cause of cancer-related mortality worldwide. Significant differences exist between Eastern and Western ... ...

Abstract	Hepatocellular carcinoma (HCC) is a heterogeneous disease that remains highly prevalent in many Asian countries and is the second most common cause of cancer-related mortality worldwide. Significant differences exist between Eastern and Western populations on many key aspects of HCC, contributing to the potential different treatment outcomes and challenges of clinical trial design and data interpretation. In this review, the authors compare HCC in Asia versus the West and highlight 1) differences in terms of epidemiology and trends and their correlation with etiology, 2) differences in genetics and how they relate to underlying etiology, 3) differences in treatment approaches based on existing guidelines and consensus statements, and 4) differences in clinical outcomes for Asian versus non-Asian patients with HCC in clinical trials and the implications for future clinical trial design. Cancer 2016;122:3430-3446. © 2016 American Cancer Society.
Language	English
Publishing date	2016-09-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.30237
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