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Background: Specialist palliative care is often provided late in the patient's disease trajectory in response to uncontrolled symptoms. Shifting from this reactionary illness-stress paradigm to a proactive health-wellness approach, the ENABLE (Educate, Nurture, Advise, Before Life Ends) telehealth model aims to enhance the coping, stress and symptom management, self-care, and advance care planning skills of patients with advanced cancers and their caregivers. The ENABLE model has been culturally adapted to Singapore (ENABLE-SG) and pilot-tested. A hybrid type 1 effectiveness-implementation design will be used to evaluate the effectiveness of ENABLE-SG while collecting real-world implementation data. Methods: This single-centre, assessor-blind, wait-list (immediately vs. 6 months) randomized controlled trial will recruit 300 adult patients within 60 days of an advanced cancer diagnosis and their family caregivers from the National Cancer Centre of Singapore. ENABLE-SG comprises structured psychoeducational sessions with a telehealth coach, covering essential topics of early palliative care. Participants will be assessed at baseline and every 3 months until patient's death, 12 months (caregivers), or end of study (patients). The primary outcome is patient quality of life 6 months after baseline. Secondary patient-reported outcomes include mood, coping, palliative care concerns, and health status. Secondary caregiver-reported outcomes include caregiver quality of life, mood, coping, and care satisfaction. Mixed-effects regression modelling for repeated measurements will be used. To assess the effectiveness of ENABLE-SG versus usual care, patient and caregiver outcomes at 6 months will be compared. To compare earlier versus delayed ENABLE-SG, patient and caregiver outcomes at 12 months will be compared. Within the hybrid type 1 effectiveness-implementation design, implementation outcomes will be evaluated in both the early and delayed groups. Acceptability, adoption, appropriateness, and feasibility will be assessed using a feedback survey and semi-structured interviews with a purposive sample of patients, caregivers, and healthcare providers. Transcribed interviews will be analysed thematically. Other implementation outcomes of penetration, fidelity, and cost will be assessed using records of study-related processes and summarized using descriptive statistics. A cost-effectiveness analysis will also be conducted. Discussion: This study will assess both effectiveness and implementation of ENABLE-SG. Insights into implementation processes can facilitate model expansion and upscaling. Trial registration: Registered prospectively on ClinicalTrials.gov, NCT06044441. Registered on 21/09/2023. [ABSTRACT FROM AUTHOR]

Context: Cost-conscious care is critical for healthcare sustainability but evidence suggests that most doctors do not consider cost in their clinical decision making. A critical step in changing this is understanding the barriers to encouraging behaviours and attitudes related to cost-conscious care. We therefore conducted a qualitative study to address the research question: what factors influence consideration of cost in emergency medicine (ED) clinical decision making? Methods: This was a qualitative focus group study using patient vignettes to explore attitudes towards cost-conscious clinical decision making. Participants were Year 4 and Year 5 medical students from Singapore, a country with a fee-for-service healthcare system. After a data-driven initial data analysis, and to make sense of a multitude of factors impacting on cost conscious care, we selected Fishbein's integrative model of behavioural prediction to underpin secondary data analysis. Results: Via four focus groups with 21 participants, we identified five main themes relevant to the integrative model of behavioural prediction. These were: attitudes towards considering cost when managing a patient (e.g., "better safe than sorry"); normative beliefs (e.g., doing what others do, perceptions of patient wishes); efficacy beliefs (e.g., no authority to take decisions or challenge); skills and knowledge (e.g., little knowledge of costs), and environmental constraints (e.g., the nature of the healthcare system). Discussion: Medical students do not consider cost in their clinical decision making due to numerous factors, of which lack of knowledge of costs is but one. While some of the factors identified reflect those found in previous studies with residents and fully-trained staff, and in other contexts, theory driven analysis added value in that it facilitated a richer exploration of why students do not consider cost in clinical decision making. Our findings provide insight to inform how best to engage and empower educators and learners in teaching and learning about cost-conscious care. [ABSTRACT FROM AUTHOR]

This article highlights the processes and best practices adopted by Nanyang Technological University (NTU) in Singapore in implementing their mission-critical e-learning services for a population of 28,000 students and 1,100 faculty members. The various phases of this rapid growth in e-learning from the initial genesis in achieving mass buy-in by professors and students through change of content type by adding a human touch to e-learning are discussed. Also included in the discussion are the additional phases in this development effort which include re-using content to make learning more efficient, achieving engaged and interactive learning in e-learning 2.0, and, most recently, a University 2.0 phase where learning becomes more participative and immersive with student life. (Contains 1 table and 7 figures.)

This paper examines the problem of a curriculum which promotes a standard linguistic variety in a context where non-standardisms are common in the learners' milieu. There have been curricula which try to incorporate the non-standard and have its function discussed; some have considered the non-standard a stepping-stone towards the standard; and yet others have tried to keep the non-standard out of the school context. We examine the Singaporean context with reference to English in the classroom, where the last option seems to be the implicit one. We focus in particular on the views of 260 upper secondary pupils in five non-elite schools, elicited through survey questionnaires. The results show that there is clear appreciation of the value of Standard English; it is, however, also clear that that the non-standard, Singlish, plays an important social role in the community; and we suggest that it might be possible to harness the non-standard in a curriculum that promotes the standard.

This paper describes the analysis of two commonly used high school (Grades 11 and 12) chemistry textbooks in Singapore to determine if the content presented in the topic of intermolecular forces is consistent with the concepts and propositional knowledge identified by the authors as essential for the learning and understanding of the topic according to the Singapore high school chemistry syllabus. The authors found that the two textbooks did not adequately discuss the electrostatic nature of intermolecular forces, and the factors influencing the polarity of bonds/molecules, hydrogen bonding and instantaneous dipole-induced dipole interactions. The insufficient coverage of the above areas may lead to students having alternative conceptions of intermolecular forces as they may have incomplete or little understanding of the concepts involved and relationships between these concepts. Thus, teachers need to analyse textbooks carefully before using the textbooks so that they can be more aware of the difficulties that students may face when reading the textbooks, and attend to these areas by careful elaboration and integration of concepts in their lessons.

The occurrence of neurotrophic tyrosine receptor kinase (NTRK) gene fusions in a wide range of tumor types presents an attractive opportunity for using a tropomyosin receptor kinase (TRK) inhibitor as cancer therapy. Recent clinical studies have demonstrated highly efficacious outcomes associated with the use of TRK inhibitors, such as larotrectinib and entrectinib in NTRK fusion‐bearing cancers, in both adult and pediatric populations. While NTRK gene fusions are commonly found in some uncommon adult and pediatric malignancies, they are also found, albeit rarely, in a wide range of more common malignancies. The potential value of testing for NTRK gene fusions in practically all advanced malignancies is underpinned by the remarkable therapeutic outcomes that TRK inhibitors offer. This requirement presents practical and financial challenges in real‐world oncological practice. Furthermore, different testing platforms exist to detect NTRK gene fusions, each with its advantages and disadvantages. It is, therefore, imperative to develop strategies for NTRK gene fusion testing in an attempt to optimize the use of limited tissue specimen and financial resources, and to minimize the turnaround time. A multidisciplinary task force of Singapore medical experts in both public and private sectors was convened in late 2020 to propose testing algorithms for adult colorectal tumors, sarcomas, non‐small cell lung cancer, and pediatric cancers, with particular adaptation to the Singapore oncological practice. The recommendations presented here highlight the heterogeneity of NTRK‐fusion positive cancers, and emphasize the need to customize the testing methods to each tumor type to optimize the workflow. [ABSTRACT FROM AUTHOR]

Background: The benefit of specialist palliative care for cancer inpatients is established, but the best method to deliver specialist palliative care is unknown. Aim: To compare a consult model versus a co-rounding model; both provide the same content of specialist palliative care to individual patients but differ in the level of integration between palliative care and oncology clinicians. Design: An open-label, cluster-randomized trial with stepped-wedge design. The primary outcome was hospital length of stay; secondary outcomes were 30-day readmissions and access to specialist palliative care. ClinicalTrials.gov number NCT03330509. Setting/participants: Cancer patients admitted to the oncology inpatient service of an acute hospital in Singapore. Results: A total of 5681 admissions from December 2017 to July 2019 were included, of which 5295 involved stage 3-4 cancer and 1221 received specialist palliative care review. Admissions in the co-rounding model had a shorter hospital length of stay than those in the consult model by 0.70 days (95%CI −0.04 to 1.45, p = 0.065) for all admissions. In the sub-group of stage 3-4 cancer patients, the length of stay was 0.85 days shorter (95%CI 0.05–1.65, p = 0.038). In the sub-group of admissions that received specialist palliative care review, the length of stay was 2.62 days shorter (95%CI 0.63–4.61, p = 0.010). Hospital readmission within 30 days (OR1.03, 95%CI 0.79–1.35, p = 0.822) and access to specialist palliative care (OR1.19, 95%CI 0.90–1.58, p = 0.215) were similar between the consult and co-rounding models. Conclusions: The co-rounding model was associated with a shorter hospital length of stay. Readmissions within 30 days and access to specialist palliative care were similar. [ABSTRACT FROM AUTHOR]

Next‐generation sequencing (NGS)‐based diagnostics have demonstrated clinical utility in predicting improved survival benefits with targeted treatment in certain cancer types, and positive cost–benefit in several healthcare systems. However, clinical adoption in Singapore remains low despite commercial availability of these diagnostics. This expert opinion review examines the key challenges to the clinical adoption of NGS‐based diagnostics in Singapore, provides recommendations on impactful initiatives to improve adoption, and also offers practical guidance on specific cancer types in which NGS‐based diagnostics are appropriate for use in Singapore. Limited patient affordability is one major challenge to clinical adoption of NGS‐based diagnostics, which could be improved by enabling patient access to more funds for specific cancer types with clear benefits. Expert opinion based on current evidence and clinical experience supports the upfront use of hotspot panels in advanced non–small cell lung cancer (NSCLC), metastatic colorectal cancer, advanced and recurrent ovarian cancer, and acute myeloid leukemia. Comprehensive genomic profiling could be considered for upfront use in select patients with NSCLC and ovarian cancer, or in refractory patients with the four cancer types. Wider adoption of NGS‐based diagnostics will improve the delivery of cancer care in Singapore and Asia‐Pacific, and thus lead to better patient outcomes. [ABSTRACT FROM AUTHOR]

This article highlights the processes and best practices adopted by Nanyang Technological University (NTU) in Singapore in implementing their mission-critical c-learning services for a population of 28,000 students and 1,100 faculty members. The various phases of this rapid growth in c-learning from the initial genesis in achieving mass buy-in by professors and students through change of content type by adding a human touch to e-learning are discussed. Also included in the discussion are the additional phases in this development effort which include re-using content to make learning more efficient, achieving engaged and interactive learning in c-learning 2.0, and, most recently, a University 2.0 phase where learning becomes more participative and immersive with student life. [ABSTRACT FROM AUTHOR]

In a short span of three years, the Nanyang Technological University (NTU) in Singapore witnessed significant growth in the adoption of e-learning. With the use of professors-friendly e-learning applications, NTU has been able to achieve critical mass buy-in by the academic staff when the e-learning take-up rate achieved 85% of the existing NTU course curriculum. As NTU moves on to celebrate the third year of e-learning, measures were taken with the careful design considerations that aimed to "humanize" e-learning, that is, make e-learning interactive and engaging with active collaborations and student learning involvement. This includes the proliferation in the use of the video talking head format synchronized with the lecture presentation, live audio-video delivery, text chat and document annotations of a lecture presentation and delivery. This paper reviews the processes NTU adopted in adding the human touch to traditional e-learning projects and serves as a good case study for other institutions with a similar aim to achieve interactive and engaged online learning. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling., Method: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC. These recommendations are made from a multidisciplinary group of lung cancer experts in Singapore with the aim of improving patient care and long-term outcomes., Results: The recommendations address the considerations in both the advanced and early-stage settings, and take into account challenges in the implementation of biomarker testing as well as the limitations of available data. Biomarker testing for both tumour tissue and liquid biopsy are discussed., Conclusion: This consensus statement discusses the approaches and challenges of integrating molecular testing into clinical practice for patients with early- to late-stage NSCLC, and provides practical recommendations for biomarker testing for NSCLC patients in Singapore.

The occurrence of neurotrophic tyrosine receptor kinase (NTRK) gene fusions in a wide range of tumor types presents an attractive opportunity for using a tropomyosin receptor kinase (TRK) inhibitor as cancer therapy. Recent clinical studies have demonstrated highly efficacious outcomes associated with the use of TRK inhibitors, such as larotrectinib and entrectinib in NTRK fusion-bearing cancers, in both adult and pediatric populations. While NTRK gene fusions are commonly found in some uncommon adult and pediatric malignancies, they are also found, albeit rarely, in a wide range of more common malignancies. The potential value of testing for NTRK gene fusions in practically all advanced malignancies is underpinned by the remarkable therapeutic outcomes that TRK inhibitors offer. This requirement presents practical and financial challenges in real-world oncological practice. Furthermore, different testing platforms exist to detect NTRK gene fusions, each with its advantages and disadvantages. It is, therefore, imperative to develop strategies for NTRK gene fusion testing in an attempt to optimize the use of limited tissue specimen and financial resources, and to minimize the turnaround time. A multidisciplinary task force of Singapore medical experts in both public and private sectors was convened in late 2020 to propose testing algorithms for adult colorectal tumors, sarcomas, non-small cell lung cancer, and pediatric cancers, with particular adaptation to the Singapore oncological practice. The recommendations presented here highlight the heterogeneity of NTRK-fusion positive cancers, and emphasize the need to customize the testing methods to each tumor type to optimize the workflow., (© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Importance: The recently published ADAURA study has posed a significant dilemma for clinicians in selecting patients for adjuvant osimertinib. Risk factors for recurrence in early-stage epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) also remain undefined., Objective: To determine clinicopathologic characteristics and recurrence patterns of resected early-stage EGFR-positive NSCLC, using wildtype EGFR as a comparator cohort, and identify features associated with recurrence., Design, Setting, and Participants: This is a cohort study including patients diagnosed with AJCC7 Stage IA to IIIA NSCLC between January 1, 2010, and June 30, 2018, who underwent curative surgical procedures at a specialist cancer center in Singapore. The cutoff for data analysis was October 15, 2020. Patient demographic characteristics, treatment history, and survival data were collated. In exploratory analysis, whole-exome sequencing was performed in a subset of 86 patients. Data were analyzed from September 3, 2020, to June 6, 2021., Exposures: Adjuvant treatment was administered per investigator's discretion., Main Outcomes and Measures: The main outcome was 2-year disease-free survival (DFS)., Results: A total of 723 patients were included (389 patients with EGFR-positive NSCLC; 334 patients with wildtype EGFR NSCLC). There were 366 women (50.6%) and 357 men (49.4%), and the median (range) age was 64 (22-88) years. A total of 299 patients (41.4%) had stage IA NSCLC, 155 patients (21.4%) had stage IB NSCLC, 141 patients (19.5%) had stage II NSCLC, and 125 patients (17.3%) had stage IIIA NSCLC. Compared with patients with wildtype EGFR NSCLC, patients with EGFR-positive NSCLC were more likely to be women (106 women [31.7%] vs 251 women [64.5%]) and never smokers (121 never smokers [36.2%] vs 317 never smokers [81.5%]). At median (range) follow up of 46 (0-123) months, 299 patients (41.4%) had cancer recurrence. There was no statistically significant difference in 2-year DFS for EGFR-positive and wildtype EGFR NSCLC (70.2% [95% CI, 65.3%-74.5%] vs 67.6% [95% CI, 62.2%-72.4%]; P = .70), although patients with EGFR-positive NSCLC had significantly better 5-year overall survival (77.7% [95% CI, 72.4%-82.1%] vs 66.6% [95% CI, 60.5%-72.0%]; P = .004). Among patients with EGFR-positive NSCLC, 2-year DFS was 81.0% (95% CI, 74.0%-86.3%) for stage IA, 78.4% (95% CI, 68.2%-85.6%) for stage IB, 57.1% (95% CI, 43.7%-68.4%) for stage II, and 46.6% (95% CI, 34.7%-57.7%) for stage IIIA. Overall, 5-year DFS among patients with stage IB through IIIA was 37.2% (95% CI, 30.1%-44.3%). Sites of disease at recurrence were similar between EGFR-positive and wildtype EGFR NSCLC, with locoregional (64 patients [16.5%] vs 56 patients [16.8%]), lung (41 patients [10.5%] vs 40 patients [12.0%]), and intracranial (37 patients [9.5%] vs 22 patients [6.6%]) metastases being the most common. A risk estimation model incorporating genomic data and an individual patient nomogram using clinicopathologic features for stage I EGFR-positive NSCLC was developed to improve risk stratification., Conclusions and Relevance: This cohort study found that recurrence rates were high in early-stage EGFR-positive NSCLC including stage IA, yet 37.2% of patients with stage IB through IIIA were cured without adjuvant osimertinib. Further studies are needed to elucidate individualized surveillance and adjuvant treatment strategies for early-stage EGFR-positive NSCLC.

Purpose: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center., Patients and Methods: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made., Results: One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors., Conclusion: Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology., Competing Interests: Aaron C. Tan Honoraria: Amgen, Thermo Fisher Scientific Travel, Accommodations, Expenses: ASLAN Pharmaceuticals, Illumina Tira J. Tan Stock and Other Ownership Interests: Immunomedics Honoraria: AstraZeneca, Roche/Genentech Consulting or Advisory Role: AstraZeneca, Lilly, Pfizer, DKSH, Novartis Speakers' Bureau: Novartis Research Funding: Bayer, Novartis, AstraZeneca, Odonate Therapeutics, Synthon Travel, Accommodations, Expenses: AstraZeneca, Eisai Matthew C. H. Ng Honoraria: MSD Oncology, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Lilly Consulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Novartis, Merck Speakers' Bureau: Lilly Research Funding: ASLAN Pharmaceuticals Travel, Accommodations, Expenses: MSD Oncology, Taiho Pharmaceutical, Bristol Myers Squibb David W. M. Tai Honoraria: Bristol Myers Squibb, Eisai Consulting or Advisory Role: Bristol Myers Squibb, Eisai Speakers' Bureau: Ipsen, Bristol Myers Squibb, Eisai, Roche Research Funding: Bristol-Myers Squibb, Sirtex Medical, Novartis. Justina Y. C. Lam Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Bayer, Merus, Bristol Myers Squibb Travel, Accommodations, Expenses: Lilly Bien-Soo Tan Research Funding: Boston Scientific Rebecca Alexandra Dent Honoraria: Roche/Genentech, AstraZeneca, Pfizer, MSD Consulting or Advisory Role: Roche, Pfizer, Merck, Eisai, AstraZeneca, Novartis Travel, Accommodations, Expenses: Roche, Pfizer, Amgen, Merck Yoon-Sim Yap Honoraria: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Consulting or Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Eisai, Lilly, Roche, Novartis Iain B. H. Tan Honoraria: Amgen, Roche, Merck Serono, MSD Consulting or Advisory Role: Amgen, Roche, Merck Serono, MSD, Novartis Research Funding: MSD Travel, Accommodations, Expenses: Merck Serono, Amgen Su Pin Choo Honoraria: Bristol Myers Squibb, AstraZeneca Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, MSD Oncology, Eisai, Roche Travel, Accommodations, Expenses: Taiho Pharmaceutical, Bristol Myers Squibb Chee-Keong Toh Stock and Other Ownership Interests: Nektar Consulting or Advisory Role: Merck, Bristol Myers Squibb/Celgene, Astellas Pharma, MSD Oncology, Roche, DKSH, Natera, Eisai, Pfizer Speakers' Bureau: Ipsen, AstraZeneca, Merck, Astellas Pharma Mohamad Farid Honoraria: Bayer Consulting or Advisory Role: Bayer N. Gopalakrishna Iyer Consulting or Advisory Role: InvitroCue Patents, Royalties, Other Intellectual Property: A device and method of providing lighting during surgeries in deep and narrow cavities Inventors: N. C. Tan, W. S. Tan, M. H. Chew, H. K. Tan, P. Sunkeri, R. S. L. Lieu, F. W. L. Loke, N. G. Iyer. PCTSG2016-050231. Licensed to Vivo Surgical Pte Ltd Wan Teck Lim Consulting or Advisory Role: Roche, AstraZeneca, MSD Oncology, Novartis, Boehringer Ingelheim Research Funding: Bristol Myers Squibb Travel, Accommodations, Expenses: AstraZeneca, Taiho Pharmaceutical Daniel S. W. Tan Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer Consulting or Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer Research Funding: Novartis, GlaxoSmithKline, AstraZeneca Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche No other potential conflicts of interest were reported.Aaron C. Tan Honoraria: Amgen, Thermo Fisher Scientific Travel, Accommodations, Expenses: ASLAN Pharmaceuticals, Illumina Tira J. Tan Stock and Other Ownership Interests: Immunomedics Honoraria: AstraZeneca, Roche/Genentech Consulting or Advisory Role: AstraZeneca, Lilly, Pfizer, DKSH, Novartis Speakers' Bureau: Novartis Research Funding: Bayer, Novartis, AstraZeneca, Odonate Therapeutics, Synthon Travel, Accommodations, Expenses: AstraZeneca, Eisai Matthew C. H. Ng Honoraria: MSD Oncology, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Lilly Consulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Novartis, Merck Speakers' Bureau: Lilly Research Funding: ASLAN Pharmaceuticals Travel, Accommodations, Expenses: MSD Oncology, Taiho Pharmaceutical, Bristol Myers Squibb David W. M. Tai Honoraria: Bristol Myers Squibb, Eisai Consulting or Advisory Role: Bristol Myers Squibb, Eisai Speakers' Bureau: Ipsen, Bristol Myers Squibb, Eisai, Roche Research Funding: Bristol-Myers Squibb, Sirtex Medical, Novartis. Justina Y. C. Lam Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Bayer, Merus, Bristol Myers Squibb Travel, Accommodations, Expenses: Lilly Bien-Soo Tan Research Funding: Boston Scientific Rebecca Alexandra Dent Honoraria: Roche/Genentech, AstraZeneca, Pfizer, MSD Consulting or Advisory Role: Roche, Pfizer, Merck, Eisai, AstraZeneca, Novartis Travel, Accommodations, Expenses: Roche, Pfizer, Amgen, Merck Yoon-Sim Yap Honoraria: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Consulting or Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Eisai, Lilly, Roche, Novartis Iain B. H. Tan Honoraria: Amgen, Roche, Merck Serono, MSD Consulting or Advisory Role: Amgen, Roche, Merck Serono, MSD, Novartis Research Funding: MSD Travel, Accommodations, Expenses: Merck Serono, Amgen Su Pin Choo Honoraria: Bristol Myers Squibb, AstraZeneca Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, MSD Oncology, Eisai, Roche Travel, Accommodations, Expenses: Taiho Pharmaceutical, Bristol Myers Squibb Chee-Keong Toh Stock and Other Ownership Interests: Nektar Consulting or Advisory Role: Merck, Bristol Myers Squibb/Celgene, Astellas Pharma, MSD Oncology, Roche, DKSH, Natera, Eisai, Pfizer Speakers' Bureau: Ipsen, AstraZeneca, Merck, Astellas Pharma Mohamad Farid Honoraria: Bayer Consulting or Advisory Role: Bayer N. Gopalakrishna Iyer Consulting or Advisory Role: InvitroCue Patents, Royalties, Other Intellectual Property: A device and method of providing lighting during surgeries in deep and narrow cavities Inventors: N. C. Tan, W. S. Tan, M. H. Chew, H. K. Tan, P. Sunkeri, R. S. L. Lieu, F. W. L. Loke, N. G. Iyer. PCTSG2016-050231. Licensed to Vivo Surgical Pte Ltd Wan Teck Lim Consulting or Advisory Role: Roche, AstraZeneca, MSD Oncology, Novartis, Boehringer Ingelheim Research Funding: Bristol Myers Squibb Travel, Accommodations, Expenses: AstraZeneca, Taiho Pharmaceutical Daniel S. W. Tan Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer Consulting or Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer Research Funding: Novartis, GlaxoSmithKline, AstraZeneca Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

Aim: Treatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population., Methods: Clinical characteristics, treatments and survival outcomes of patients with LSCC were analysed. Baseline comorbidity data was collected and age-adjusted Charlson Comorbidity Index (aCCI) was calculated. Outcomes of overall survival (OS), progression-free survival (PFS) and laryngectomy-free survival (LFS) were evaluated., Results: Two hundred and fifteen patients were included, 170 (79%) underwent primary radiation/ chemoradiation and the remainder upfront surgery with adjuvant therapy where indicated. The majority of patients were male, Chinese and current/ex-smokers. Presence of comorbidity was common with median aCCI of 3. Median OS was 5.8 years. On multivariable analyses, high aCCI and advanced nodal status were associated with inferior OS (HR 1.24 per one point increase in aCCI, P<0.001 and HR 3.52; p<0.001 respectively), inferior PFS (HR 1.14; p = 0.007 and HR 3.23; p<0.001 respectively) and poorer LFS (HR 1.19; p = 0.001 and HR 2.95; p<0.001 respectively). Higher tumor (T) stage was associated with inferior OS and LFS (HR 1.61; p = 0.02 and HR 1.91; p = 0.01 respectively)., Conclusion: In our Asian population, the presence of comorbidities and high nodal status were associated with inferior OS, PFS and LFS whilst high T stage was associated with inferior LFS and OS., Competing Interests: The authors have declared that no competing interests exist.

Lung cancer is the leading cause of cancer-related death around the world, being the top cause of cancer-related deaths among men and the second most common cause of cancer-related deaths among women in Singapore. Currently, no screening programme for lung cancer exists in Singapore. Since there is mounting evidence indicating a different epidemiology of lung cancer in Asian countries, including Singapore, compared to the rest of the world, a unique and adaptive approach must be taken for a screening programme to be successful at reducing mortality while maintaining cost-effectiveness and a favourable risk-benefit ratio. This review article promotes the use of low-dose computed tomography of the chest and explores the radiological challenges and future directions., (Copyright: © Singapore Medical Association.)

Introduction: We reviewed changes in clinical characteristics, treatment and survival of lung cancer patients in Singapore over the past decade., Materials and Methods: We reviewed all primary lung cancer cases from January 2004 to December 2013. Basic demographic, clinical and treatment data were extracted from the database. Overall survival (OS) was calculated using Kaplan-Meier method; survival curves were compared using log-rank test. Linear regression trend lines were estimated using least squares approach, and Cox regression analyses were performed to identify prognostic factors., Results: Among 6006 lung cancer patients, the median age was 68 years old, 65% were males, 88% were Chinese, 92% had non-small-cell lung cancer and 76% had advanced stage IIIB/IV. There were proportionally more adenocarcinomas diagnosed over the years, while that of squamous cell carcinoma (SCC) and small-cell-lung cancer (SCLC) have remained stable. The median OS of all patients increased from 9.2 months in 2004 to 11.5 months in 2013. This survival improvement was statistically significant among patients with stage IIIB/IV (6.7 to 8.7 months; P = 0.005) and adenocarcinoma (12.7 to 15.4 months; P = 0.041). There was no improvement in median OS for SCC or SCLC. The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) (hazard ratio [HR] 0.68; 95% CI, 0.63 to 0.73) and pemetrexed (HR, 0.69; 95% CI, 0.63 to 0.76) were significantly associated with improved OS., Conclusion: Survival of patients with advanced stage IIIB/IV lung adenocarcinoma has improved over the past decade, and is potentially associated with the use of EGFR TKI and pemetrexed.

Background: P16 and cyclin-D1 are cell cycle proteins commonly dysregulated in head and neck carcinoma. We assessed their expression, clinicopathological variables, and overall survival (OS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC)., Methods: Clinical characteristics and p16 and cyclin-D1 expression were evaluated in 101 patients with oropharyngeal SCC and 75 patients with hypopharyngeal SCC. Associations with OS were assessed using Cox regression and Kaplan-Meier analysis., Results: Compared to oropharyngeal SCC, patients with hypopharyngeal SCC were older, men, ever-smokers with higher mean Charlson Comorbidity Index (CCI), lower p16 expression, and poorer median OS (24.8 vs 62.3 months; p < .01). In oropharyngeal SCC, CCI (p < .001), cyclin-D1 (hazard ratio [HR] = 3.55; p = .007), current smoking (HR = 5.72; p = .004), and former smoking (HR = 4.12; p = .035) were independently associated with OS. In hypopharyngeal SCC, only nodal and Eastern Cooperative Oncology Group status were associated with OS., Conclusion: In oropharyngeal SCC, cyclin-D1 expression is correlated with survival, whereas smoking status and CCI may allow further stratification of outcome., (© 2014 Wiley Periodicals, Inc.)

Background: Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention., Methods: Seventy-eight cases were subjected to whole-exome (n = 18) and targeted deep sequencing (n = 60)., Results: While the most common mutation was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck tumors: OTSCCs demonstrated frequent mutations in DST and RNF213, while alterations in CDKN2A and NOTCH1 were significantly less frequent. Despite a lack of previously reported NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling in OTSCC. Importantly, these Notch pathway alterations were prognostic on multivariate analyses. A high proportion of OTSCCs also presented with alterations in drug targetable and chromatin remodeling genes. Patients harboring mutations in actionable pathways were more likely to succumb from recurrent disease compared with those who did not, suggesting that the former should be considered for treatment with targeted compounds in future trials., Conclusions: Our study defines the Asian OTSCC mutational landscape, highlighting the key role of Notch signaling in oral tongue tumorigenesis. We also observed somatic mutations in multiple therapeutically relevant genes, which may represent candidate drug targets in this highly lethal tumor type.

Background: Epidermal growth factor receptor (EGFR) testing and first-line therapy with gefitinib for patients with activating mutations is quickly becoming the standard option for the treatment of advanced lung adenocarcinoma. Yet, to date, little is known about the cost-effectiveness of this approach., Methods: A decision-analytic model was developed to determine the cost-effectiveness of EGFR testing and first-line treatment with gefitinib for those patients who harbor activating mutations versus standard care, which includes first-line treatment with chemotherapy followed by gefitinib as second-line treatment. The model uses clinical and outcomes data from randomized clinical trials and societal costs from Singapore cancer centers. Health effects were expressed as quality-adjusted life-years. All costs and cost-effectiveness ratios were expressed in 2010 Singapore dollars. Sensitivity and different scenarios analyses were conducted., Results: EGFR testing and first-line treatment with gefitinib is a dominant strategy (with lower costs and greater effectiveness) compared with standard care. Because the primary savings result from not providing gefitinib to those who are not likely to benefit, this finding holds regardless of the prevalence of activating mutations. In a secondary analysis, first-line treatment with gefitinib was also dominant when compared with first-line chemotherapy in patients with activating EGFR mutations., Conclusions: This strategy can be considered a new standard of care and should be of great interest for health care payers and decision makers in an era in which our greatest challenge is to balance hard-won and incremental, yet small, improvements in patient outcomes with exponentially rising costs., (Copyright © 2011 American Cancer Society.)

The use of rituximab has been associated with increased risk of hepatitis B virus (HBV) reactivation in patients who are hepatitis B surface antigen (HBsAg) negative and antihepatitis B core antibody (anti-HBc) positive. We aim to determine the rate of HBV reactivation in this group of patients who received rituximab-containing combination chemotherapy without concomitant antiviral prophylaxis and to identify potential risk factors for reactivation. Sixty-two HBsAg negative/anti-HBc positive patients with B-cell lymphoma treated with rituximab-based immunochemotherapy from 2006 to 2009 were included. None of the patients received concomitant antiviral prophylaxis. In this cohort, 48 (77%) patients received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), eight (13%) received rituximab with cyclophosphamide, vincristine and prednisolone, and six (10%) received other chemotherapy regimens. Two patients suffered HBV reactivation; both were above 70 years of age, received R-CHOP chemotherapy and were negative for antihepatitis B surface antibody (anti-HBs) at baseline. One of the two patients reactivated shortly after completion of R-CHOP chemotherapy while the other reactivated during rituximab maintenance treatment. Thus, the overall reactivation rate in this cohort of patients is 3% (2/62), 4% (2/48), and 25% (1/4) in patients who received R-CHOP chemotherapy and who received rituximab maintenance, respectively. The rate of HBV reactivation is low in patients who are HBsAg negative/anti-HBc positive receiving rituximab-based combination chemotherapy without concomitant antiviral prophylaxis. However, elderly patients, particularly those without anti-HBs, seemed particularly at risk.