University Malaya Medical Centre Research Articles

Survival analysis of osteosarcoma patients: A 15-year experience.

Management of osteosarcoma has evolved considerably for the past two decades and there have been changes of practices especially pertaining to chemotherapy regime. This is a review of our cases in the past 15 years. This is a retrospective survival analysis study of 128 patients treated at University Malaya Medical Centre (UMMC) from 1997 to 2011. There were 80 (62.5%) male and 48 (37.5%) female patients with the median age being 15 (5-59). Majority had osteosarcoma of extremities (94.5%). More than 60% patients developed metastasis throughout the course of treatment with 39% presenting with lung metastasis. Osteoblastic osteosarcoma was the commonest subtype (65.6%). Of the 109 patients treated surgically, 84 patients (65.6%) underwent limb salvage surgery while the rest underwent amputation. Seventy-one per cent of patients completed treatment with local recurrence rate of 22.7%. The 5-year and 10-year survival rates were 56.31% (95% CI: 46.20, 65.24) and 22.33% (95% CI: 14.86, 30.76), respectively. The 5-year event-free survival was 52.94% (95% CI: 41.83, 62.87). In multivariate analysis, the independent prognostic factors were presence of metastasis and completion of treatment for both 5-year and 10-year overall survival. Good histological response was only significant for multivariate analysis at 5 years. Patients with metastasis had a hazard ratio of 20.4 at 5 years and 3.26 at 10 years. Overall survival rate for osteosarcoma patients at our centre was comparably higher than other centres in the region. Two independent risk factors for survival are metastatic status and completion of treatment. A standardized chemotherapy regime is essential for long-term survival.

54 Patient Safety Culture at a Teaching Hospital in Kuala Lumpur

Abstract Introduction Patient safety, such as inpatient falls, is a global problem, accounting for increasing compensation costs from our healthcare facilities. The aim of this study was to evaluate the patient safety culture among healthcare providers. Method An online survey was developed within the hospital staff portal at the University of Malaya Medical Centre, with a dialogue box appearing on the launching of the portal website inviting the members of staff to participate in the survey. The survey contained a safety assessment questionnaire (SAQ) which measures the patient safety culture. The SAQ consists of 36 items measuring the six domains: teamwork climate, job satisfaction, safety climate, stress recognition, working conditions, and perception of management. Each domain is assigned a percentage score, and comparisons of scores according to healthcare disciplines were then made. Results 5275 (80%) responded to the online SAQ which was sent out to all 6562 healthcare professionals employed, by the hospital. The teamwork and safety climate was poor among supporting staff, with scores of 56.7 and 59.8 respectively. Job satisfaction (62.9), perception of ward management (56.8), and hospital management (53.2), and working conditions (44.7) were less among the clinicians. Stress recognition (36.5) was in alarmingly low among the nurses. Conclusion A comprehensive unit-based safety programme will be conducted in response to the SAQ findings, and should incorporate objective falls the outcome in order to convince the hospital hierarchy of the need for urgent solutions to lower the rates of inpatient falls.

46 The Relationship between Cognitive Function and Physical Performance among Older Adults Attending a Falls and Syncope Service in Kuala Lumpur

Abstract Introduction Recent studies identified a relationship between gait difficulties and risk of developing dementia, a condition now termed motoric cognitive risk. We interrogated a clinical dataset to determine the relationship between cognitive assessment scores and physical performance scores to identify the strength of association between these two types of measures. Methods Consecutive patients referred to the falls and syncope service and the University of Malaya Medical Centre were recruited. The cognitive function of consenting individuals was assessed using the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Tool (VCAT). Physical performance was assessed using hand grip strength (HGS), timed-up-and-go (TUG) and functional reach (FR). Results One hundred and forty-seven individuals, mean age (standard deviation,SD)=76.1 (7.8) years, 85 (58%) women were included. The mean (SD) for right and left HGS, FR and TUG scores for the overall population were 19.1 (7.0)kg, 19.0 (12.1)kg, 28.9 (39.7)cm, TUG 19.2 (11.0)s respectively. The mean MoCA and VCAT scores were 21.1 (7.1) and 20.3 (6.3) respectively. Right HGS correlated moderately with MoCA (r=0.367) and VCAT scores (r=0.397). Left HGS had a weak to moderate correlation with MoCA (r=0.281) and VCAT (0.271). FR, however, was not correlated with either MoCA (r=0.073) and VCAT (0.020). TUG scores were moderately negatively correlated with MoCA (-0.3206) but weakly correlated with VCAT (-0.175) Conclusion Our evaluation of the relationship between cognitive scores and physical performance in a falls and syncope clinic setting found that a relationship exists between muscle strength measured with grip strength and composite assessment of gait and balance using the TUG. Dynamic balance measured with functional reach, however, was not associated with cognitive function. Future studies will need to identify the possible mechanisms linking cognitive function with strength and gait in order to establish cognitive function as a modifiable risk factor for falls in older adults.

102 Why Aren’t Malaysian Elderly Attending a Falls Prevention Education Intervention (FPEI)? An Exploratory Study.

Abstract Background Recent studies on barriers and facilitators to implementation of falls prevention education interventions (FPEIs) are conducted in the developed countries. Hence, the findings may limit its transferability when implementing FPEI for elderlies in countries of different culture and healthcare systems. This study explored barriers and facilitators which have impacted the elderlies who have attended a locally developed FPEI. Methods A qualitative methodology was adopted. Seventeen individuals aged 60 years and over with at least one fall in the preceding 12 months and have attended FPEI were recruited. Three focus group discussions were conducted at the Primary Care Clinic, University Malaya Medical Center (UMMC), Kuala Lumpur. With the aid of a semi-structured interview guide, interviews were conducted immediately after attending the FPEI. The interviews were audio-recorded, transcribed verbatim and analyzed using a thematic approach using the Weft QDA software. Results Participants were predominantly females (n=12) in their mid-70s, consisting of seven Indians, four Malays and six Chinese. Five themes emerged, and they were the accessibility of the infrastructures, favorable timing, the involvement of interprofessional, FPEI content, and stretching and balance exercises. The FPEI attendees interviewed did not prefer the venue which was located far from the hospital entrance, some claimed that the FPEI should be held together with their hospital consultation visit, while others felt that the involvement of interprofessional improved their engagement with the FPEI. Some elderlies felt that the information on falls risks, falls preventions, and stretching and balance exercises informed by the FPEI imparted new knowledge; however, others perceived that they already undertake strenuous exercises. Conclusions When implementing FPEI, it is crucial to consider the elderlies’ logistics and the existence of falls knowledge particularly in developing countries such as Malaysia where concepts of FPEI are still novel.

The Effect of 20-Minute Mindful Breathing on the Perception of Suffering and Changes in Bispectral Index Score (BIS) in Palliative Care Informal Caregivers: A Randomized Controlled Study.

Informal caregivers are at risk of being overwhelmed by various sources of suffering while caring for their significant others. It is, therefore, important for caregivers to take care of themselves. In the self-care context, mindfulness has the potential to reduce caregiver suffering. We studied the effect of a single session of 20-minute mindful breathing on the perceived level of suffering, together with the changes in bispectral index score (BIS) among palliative care informal caregivers. This was a randomized controlled study conducted at the University of Malaya Medical Centre, Malaysia. Forty adult palliative care informal caregivers were recruited and randomly assigned to either 20-minute mindful breathing or 20-minute supportive listening. The changes in perceived suffering and BIS were measured preintervention and postintervention. The reduction in suffering score in the intervention group was significantly more than the control group at minute 20 (U = 124.0, n1 = n2 = 20, mean rank1 = 24.30, mean rank2 = 16.70, z = -2.095, P = .036). The reduction in BIS in the intervention group was also significantly greater than the control group at minute 20 (U = 19.5, n1 = n2 = 20, mean rank1 = 29.52, mean rank2 = 11.48, z = -4.900, P < .0001). Twenty minutes of mindful breathing was more efficacious than 20 minutes of supportive listening in the reduction in suffering among palliative care informal caregivers.

Obstructive sleep apnoea and open heart surgery: a review of its incidence and impact to patients.

Obstructive sleep apnea (OSA) is a serious health disorder which contributes to cardiovascular complications, decreased work productivity, automobile accidents, and death. This condition is characterized by a temporary cessation of breathing resulting due to upper airway closure during a person's sleep. Strain to the heart caused by this repetitive hypoxic insult can lead to postoperative complications for patients undergoing heart surgery. Recognizing cardiac surgical patients with OSA is important. Early recognition and intervention such as use of BiPAP device can reduce the postoperative complications due to OSA. The aim of this study is to identify the incidence of unrecognized OSA in cardiac surgical patients. This is a retrospective analysis of a prospective data of the study which was done between July 2012 and July 2013 in University Malaya Medical Center. All patients undergoing elective cardiac surgery were recruited and the demographic data, questionnaire and the portable sleep study results were obtained. Patients were followed up till 30 days to record any complications. Data were entered in SPSS version 17 and analysis was done. The incidence of OSA was 61.4% and 43.5% were moderate to severe OSA. There was male predominance of OSA (79%) with a mean age of 60 years. OSA subjects had shorter inter-incisor distance (4.18±0.6 cm) and larger waistline (94.1±12.1 cm). The STOP-Bang questionnaire has a sensitivity of 75.8% in predicting apnoa-hypopnea index (AHI) ≥5/hour. OSA can be diagnosed with a simple screening questionnaire and a bedside portable sleep study. Cardiac patients diagnosed with OSA can be pre-emptively given extra attention in managing their postoperative care.

Quality of Life and Treatment Satisfaction Among Patients on Long Term Oral Anticoagulant in A Developing Country

Background: Randomised phase III studies had proven the efficacy and safety profile of direct oral anticoagulant (DOAC) over warfarin in stroke and systemic embolism prevention for patients with atrial fibrillation (AF) and venous thromboembolism (VTE). Nevertheless, patients’ quality of life (QOL) and treatment satisfaction was not explored in these studies. Objective: The primary objective of this study was to compare the QOL and treatment satisfaction of patients on long term warfarin versus DOACs in a tertiary hospital in Malaysia. Methods: This is a cross-sectional study of patients with nonvalvular AF (NVAF) or VTE on long term warfarin versus DOACs attending the cardiology clinic and anticoagulation clinic of University Malaya Medical Centre from 1 st July 2016 to 30 st June 2018. Patients’ QOL was assessed by using Short Form 12v2 Health Survey (SF12v2); while treatment satisfaction was assessed by using Perception of Anticoagulation Treatment Questionnaire 2 (PACT-Q2). Results: Of 208 patients, 52.4% received warfarin and remaining 47.6% received DOACs. The warfarin group was significantly younger and had longer treatment duration (p b 0.001); while DOAC group had significant more underlying NVAF (p b 0.001) and polypharmacy (p= 0.003). There was no significant difference in the score of physical component summary (PCS) (p= 0.083), mental component summary (MCS) (p = 0.665) and each domain of SF-12v12 (p = 0.058 – 0.953) between anticoagulant groups. There were no differences between the 2 groups of anticoagulants even after adjustment of age. The satisfactionscore was significant higher in DOACs group compared to warfarin group (p = 0.003); but there was no difference in the convenience score (p= 0.234). Hospitalisation rate was significantly higher (p = 0.002) in warfarin group. Only 45.0% of patients achieved good time in therapeutic range (TTR). Conclusions: Despite no significant difference in QOL, patients with AF or VTE who were treated with DOACs demonstrated better efficacy, safety, and satisfaction profile, as well as a relatively stable within-group QOL.

Metabolic Syndrome Is Associated With Advanced Liver Fibrosis Among Pediatric Patients With Non-alcoholic Fatty Liver Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) among children is a growing concern with potential significant outcome. This study aims to investigate the relationship between hepatic steatosis, metabolic syndrome, and liver fibrosis among children with obesity and diabetes mellitus.Methodology: Children aged 6–18 years old were recruited from pediatric obesity and diabetes clinic in University Malaya Medical Center (UMMC) between year 2016 and 2019. Data on basic demographics, anthropometric measurements and clinical components of metabolic syndrome were collected. Transient elastography was performed with hepatic steatosis and liver fibrosis assessed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) respectively. Mild, moderate and severe steatosis were defined as >248, >268, and >280 dB/m respectively, and LSM above 7.0 kPa for fibrosis stage F ≥ 2, 8.7 kPa for F ≥ 3, and 10.3 kPa for F4 (cirrhosis).Results: A total of 57 children (60% male) with median age of 13 years old were recruited. Fifty (87.7%) of the children are obese and 27 (54%) out of 50 are morbidly obese. Among 44 (77.2%) patients with steatosis, 40 (70.2%) had severe steatosis and 18 (40.9%) had developed liver fibrosis of stage 2 and above. Advanced fibrosis or cirrhosis was detected in 8 (18.2%) children with presence of steatosis. Twenty-three out of 57 (40.4%) was diagnosed with metabolic syndrome. Fibrosis is three times more likely to occur in the presence of metabolic syndrome (OR = 3.545, 95% CI: 1.135–11.075, p = 0.026). Waist circumference is a significant predictor of fibrosis after multiple regression analysis.Conclusion: Obese children with metabolic syndrome are more likely to have advanced liver fibrosis compared to those without metabolic syndrome. Waist circumference predicts development of liver fibrosis.

Causative factors of eating problems among adolescents with type 1 diabetes mellitus: A qualitative study.

Adolescents with type 1 diabetes mellitus are prone to have eating problems. This study aimed to determine factors of eating problems among this population in University Malaya Medical Centre. Fifteen adolescents who scored more than 20 marks in the Diabetes Eating Problem Survey - Revised questionnaire were invited for an in-depth interview. Questions were asked based on their questionnaire's response. The interview sessions were recorded, transcribed verbatim, and thematic analysis was used. Five main themes emerged: pressure, physiological factor, psychological factor, patient's low compliances to insulin intake and food control and fear. Early referral to child psychologist would prevent it from developing.

Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma.

Endoscopic endonasal nasopharyngectomy (EEN) for recurrent nasopharyngeal carcinoma (rNPC) is being increasingly used due to the added high magnification, reduced morbidities associated with open procedures and good survival outcomes. Most studies looked at usage of EEN in patients with lower recurrent staging (rT1 and rT2) although more and more surgeons are studying the outcome of EEN in advanced rNPC (rT3 and rT4). The aims of this study were to report the long-term 5-year survival outcome of EEN performed in patients with advanced rNPC, and to determine any prognostic factors for patients' survival. All patients who underwent EEN for advanced rNPC between January 2003 and December 2015 inclusive were analyzed. All surgeries were performed in University Malaya Medical Centre in Kuala Lumpur and Queen Elizabeth Hospital in Sabah. We reported the 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and any related complications and significant prognostic factors. Twelve patients with rNPC (2 rT3 and 10 rT4) were followed-up over a mean duration of 44.8 months (range, 40-440 weeks). The 5-year OS was 50.0% (mean 44.75 months), DFS was 25.0% (mean 35.25 months) and the DSS was 58.3% (mean 43.33 months). No severe operative complications were encountered and no independent prognostic factors for survival outcome were identified. This is the first report in English that exclusively described the long-term 5-year survival data in patients with both rT3 and rT4 recurrent NPC after EEN. The data suggest that EEN is a feasible treatment to improve survival with minimal morbidities in patients with rT3 and rT4 recurrent NPC. However, more studies with larger patient size is recommended.

373P - Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)

BackgroundThere is an expanding list of therapeutically relevant biomarkers for NSCLC and effective molecular profiling is paramount. We sought to comprehensively and prospectively evaluate the molecular epidemiology of NSCLC in Asia and ascertain the extent of access to relevant therapies. The study is being conducted by the Asian Thoracic Oncology Research Group (ATORG) – an academic co-operative lung cancer trials group in Asia. MethodsATORG-001 is a prospective, multi-centre study of NSCLC patients (pts) throughout Asia. Eligible pts must have good performance status (ECOG ≤2), adequate organ function and ≤3 prior lines of cytotoxic chemotherapy. Archival tissue specimens are sent to a central laboratory in Singapore (Singapore General Hospital) for profiling, consisting of NGS with the Oncomine Focus Assay (52 gene panel including fusions) and PD-L1 immunohistochemistry. Results are returned to investigators in a clinically relevant timeframe. Baseline demographics, pre-existing molecular profile and prior treatment details are collected. Treatment and pt outcomes are followed for 2 years. Recruitment commenced in Jan 2019 in 3 sites (National Cancer Centre Singapore, Chinese University of Hong Kong, University Malaya Medical Centre). We report an interim analysis for the first 27 of a planned 500 pts. ResultsAs of 01 Jul 2019, 27 pts have enrolled with median age 67 yrs (range 46-79), 59% male, 81% adenocarcinoma, 52% stage IV, 37% non-smokers, median lines of prior therapy 1 (range 0-6) and 85% with no known oncogenic driver. Pre-existing mutation status was known in 89% for EGFR and 63% for ALK. Median turnaround time from tissue acquisition to profiling results was 22 days (range 15-74). New alterations were most common in KRAS (19%), MYC (15%), CDK4 (7%) and ERBB2 (7%). Potentially actionable new alterations were found in 7 (26%) pts, including KRAS G12C mutation (7%), BRAF G469A mutation (4%), ERBB2 exon 20 insertion (4%), ERBB2 amplification (4%), FGFR2 amplification (4%) and MET exon 14 skipping mutation (4%). ConclusionsEnrolment is ongoing with additional sites and countries planned to comprehensively evaluate the molecular epidemiology of NSCLC in Asia. Legal entity responsible for the studyAsian Thoracic Oncology Research Group. FundingAsian Thoracic Oncology Research Group, Novartis. DisclosureA.C. Tan: Travel / Accommodation / Expenses: ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest.

487P - Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma

BackgroundAfatinib is an irreversible second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) while gefitinib or erlotinib are reversible first-generation EGFR-TKIs. MethodsA retrospective analysis of patients with EGFR mutant advanced lung adenocarcinoma receiving first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. ResultsOf 113 patients, 24 (21.2%) received afatinib, 63 (55.8%) received gefitinib and 26 (23.0%) received erlotinib in first-line setting. Their demographic and clinical characteristics are shown in the table. Afatinib was used significantly more frequently in patients with rare or complex EGFR mutations (p = 0.005), and more often in patients with symptomatic brain metastases. The median progression-free survival (mPFS) of patients treated with afatinib (13.1 months) was longer than that of patients treated with gefitinib (10.9 months) or erlotinib (7.8 months) (p = 0.479). Patients receiving afatinib had consistently longer PFS than patients receiving gefitinib for the first 17 months and erlotinib for the first 20 months. The overall response rate was higher in patients on afatinib (75.0%) than those on gefitinib (63.5%) or erlotinib (53.8%). There was no difference in the disease control rate. Three patients (2.7%) had severe side-effects while on EGFR-TKI. Of two patients on afatinib, one had grade-3 diarrhea while another had grade 3 stomatitis, rash and paronychia. One patient had grade 3 rash on gefitinib.Table487P Clinical characteristic of 113 patients on first-line EGFR-TKITableCharacteristics, No (%)Afatinib (24)Gefitinib (63)Erlotinib (26)p-valueSymp brain metsNo Yes17 (70.8) 7 (29.2)53 (84.1) 10 (15.9)22 (84.6) 4 (15.4)0.181EGFR subtype19 del 21 L858R Rare/complex16 (66.7) 2 (8.3) 6 (25.0)39 (61.9) 20 (31.7) 4 (6.3)22 (84.6) 3 (11.5) 1 (3.8)0.005Side-effectgrade 1-2 grade 322 (91.7) 2 (8.3)62 (98.4) 1 (1.6)26 (100) 00.007Objective responseYes No18 (75.0) 6 (25.0)40 (63.5) 23 (36.5)14 (53.8) 12 (46.2)0.298Disease controlYes No23 (95.8) 1 (4.2)59 (93.7) 4 (6.3)24 (92.3) 2 (7.7)0.872Median PFSMonths Event, No. (%)13.1 19 (79.2)10.9 49 (77.8)7.8 19 (73.1)0.479 ConclusionsPatients receiving first-line afatinib demonstrated longer mPFS than those on first-line gefitinib or erlotinib. The lack of statistical significance in this study is because of the small number of patients treated with afatinib, more frequent rare or complex EGFR mutations and more symptomatic brain metastases among afatinib treated patients. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

494P - Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

BackgroundPatients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. MethodsA retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. ResultsOf 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib.Table494PTablePattern of PDPatients with PD (n = 87)Afatinib (n = 19)Gefitinib (n = 49)Erlotinib (n = 19)p-valueMedian PFS, months11.013.110.97.80.479New brain metastases, No. (%)Yes No20 (23.0) 67 (77.0)5 (26.3) 14 (73.7)12 (24.5) 37 (75.5)3 (15.8) 16 (84.2)0.692New solid brain lesion metastases, No (%)Yes No19 (21.8) 68 (78.2)4 (21.1) 15 (78.9)12 (24.5) 37 (75.5)3 (15.5) 16 (84.2)0.735New leptomeningeal metastases, No. (%)Yes No4 (4.6) 83 (95.4)1 (5.2) 18 (94.8)3 (6.1) 46 (93.9)0 19 (100)0.550No. of patients tested for acquired T790M mutationn = 49n = 14n = 27n = 8p-valueAcquired T790M mutation detected, No. (%)Yes No30 (61.2) 19 (38.8)9 (64.3) 5 (35.7)16 (59.3) 11(40.7)5 (62.5) 3 (37.5)0.949 ConclusionsNew leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Lenvatinib, In Treating Advanced Malignant Thyroid Tumours, Real Life Experience from University Malaya Medical Centre

Abstract Background Differentiated thyroid cancer (DTC) is the commonest endocrine cancer in Malaysia. Chemotherapy and radiotherapy has limited role in managing radioactive iodine (RAI)-refractory DTC. With the understanding of the molecular profiling of DTC, various novel therapies have been developed. Lenvatinib is a multiple kinase inhibitor (MKI) with promising activities based on the randomized phase III SELECT trial. Our study was to evaluate the safety and efficacy of lenvatinib a real live experience in patients with metastatic RAI-refractory DTC from University Malaya Medical Centre. Methods RAI-refractory DTC patients with progressive disease and with good performance status (0-2) were screened and treated with lenvatinib at UMMC from November 2014 to April 2017 with Eisai Named Patient Assisted Programme (NPAP) and the data was collected and analysed. Data collection was ended on June 2018. Results There were 23 patients with a median of 65 years (31-76) were enrolled. The male: female ratio was 1:1. All patients had prior thyroid surgery with history of at least once RAI treatment. Only 2 patients (8.7%) had prior therapy with sorafenib. Commonest sites of metastases were lung and bones. 47% of patients showed positive clinical response and 8.7% showed radiological response and 82.6% has biochemical response. Median overall survival (OS) was not ready to be calculated, and median progression free survival (PFS) was 23.9 months. Common adverse events (AE) observed in all grades were hypertension (87.0%), fatigue (95.7%), proteinuria (69.6%), skin reactions (52.2%) and diarrhoea (43.5%). Almost all cases had dose interruptions and reductions due to AE and it was done within initial 2 months of therapy. 26.7% of patients are still on the treatment. Conclusions Lenvatinib is a new treatment option with significant clinical benefit for patients with metastatic RAI-refractory DTC. It has significant adverse events but manageable toxicity with dose interruptions.

EP1.14-17 Acquired T790M Mutation in Patients Failing Treatment with First or Second-Generation EGFR-Tyrosine Kinase Inhibitors

Background: The majority of patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC) develop resistance to first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) after a median treatment period of 12 months. This study aimed to determine the prevalence and predictors of acquired T790M mutation as a resistance mechanism among these patients. Method: This was a retrospective study of patients with sensitising EGFR-mutant advanced NSCLC who experienced disease progression (PD) while on first- or second-generation EGFR-TKI treatment and underwent investigations to determine the resistance mechanisms in University of Malaya Medical Centre from 1st January 2015 to 31st December 2017. Result: Of 87 patients, acquired T790M mutation was detected in 55 (63.2%) patients at PD. T790M mutation was significantly more frequent in patients who achieved partial response (PR) as the best response (p ¼ 0.008) or had new lung metastasis (p ¼ 0.048); and significantly less frequent in patients who developed new symptomatic brain metastases (p ¼ 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p ¼ 0.077). In multivariate analysis, PR with EGFR-TKI treatment was a significant independent predictor of acquired T790M mutation (p ¼ 0.021) while having new symptomatic brain metastases (p ¼ 0.034) or new lymph node metastases (p ¼ 0.038) were significant independent predictors against acquired T790M mutation. Conclusion: Acquired T790M mutation was a common resistance mechanism leading to first- or second-generation EGFR-TKI treatment failure. Patients with tumours harbouring exon 19 deletion mutation were more likely to acquire T790M mutation. A best tumour response of PR to EGFR-TKI treatment was an independent predictor of acquiring this resistance. This information is helpful to clinicians in the early prognostication and management planning for patients with EGFR-mutant NSCLC.

Chemotherapy Induced Nausea and Vomiting and Quality of Life of Patients On Moderate And Highly Emetogenic Chemotherapy

Abstract Background Chemotherapy-induced nausea and vomiting (CINV) in cancer treatment are symptoms most feared by patients (pts). The study aim is to analyze the impact of CINV associated to moderately (MEC) or highly emetogenic chemotherapy (HEC) regimes on pts’ quality of life (QOL). Methods Prospective observational study was done among pts receiving MEC or HEC in University Malaya Medical Center. 88 patients (pts) fulfilled the inclusion criteria. Pts were prescribed standard antiemesis based on national guidelines. Each pt filled up a diary for each cycle from the day before chemotherapy up to day 5 days which included details of emesis history. Pts completed the self-report European Organization for Research and Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) before chemotherapy (baseline) and day 5 after each cycles, for 3 consecutive cycles. To estimate the effects of CINV on QOL, the change in scores between the baseline and day 5 HQL assessments was calculated for each domain the QLQ-C30 and compared in 3 subgroups of pts: 1) with both nausea and vomiting, 2) with nausea but no vomiting, 3) with neither nausea nor vomiting. Results Total of 33 pts (37.5%) develop vomiting during cycle 1, 34 (38.6%) in cycle 2 and 38 (43.2%) in cycle 3. For nausea, 50 pts (56.8%) developed nausea cycle 1, 58 patients (65.9%) in cycle 2 and 3. The incidence of vomiting is higher in female (p-value Conclusion The study demonstrated a significant no of pts who underwent MEC or HEC suffered CINV despite the use of standard anti-emetics treatment. We demonstrated that pts who did not suffer from CINV have better QOL.

Development of Steatohepatitis and Fibrosis in Chronic HBV Infection Is Linked to Inflammatory Responses Mediated by IL-13 and CCL11

Background: In view of the importance of chronic HBV (CHB) infection and the global burden of non-alcoholic fatty liver disease (NAFLD), it is imperative to understand the potential interplay between the two diseases. Methods: Here, we retrospectively investigated the association between NAFLD and CHB infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between year 2013 and 2016, we studied 449 subjects in the current investigation. Findings: CAP and LSM scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the HBV viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. Interpretations: Together, we found that there was a high concurrence of NAFLD among patients with CHB. The presence of metabolic syndrome and chronic inflammation in CHB patients were two independent factors that led to progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components. Plasma markers of liver steatosis and fibrosis progression are key to development of cell-targeted therapies exploiting specific molecular pathways. Funding Statement: This work was supported by a grant from the Frontier Research Grant (FRG), FG019-17AFR to Mohamed Rosmawati and Xiamen University Malaysia Research Funding (XMUMRF), XMUMRF/2018-C2/ILAB/0001. Marie Larsson is supported by the Swedish Research Council, the Swedish Physicians against AIDS Research Foundation; VINNMER for Vinnova, Linkoping University Hospital Research Fund, ALF Grants Region Ostergotland, FORSS. Declaration of Interests: The authors declare no conflicts interest. Ethics Approval Statement: The medical records of patients were extracted from the hospital database using patients’ unique hospital registration number. This study was approved by the Medical Ethics Committee of the University Malaya Medical Centre (MEC-938.42).

Haematopoietic stem cell transplantation for inborn errors of immunity: 25-year experience from University of Malaya Medical Centre, Malaysia.

Inborn errors of immunity (IEI) comprise a heterogeneous group of disorders of the immune system, most of which are curable by haematopoietic stem cell transplantation (HSCT). We present a 25-year audit of HSCT for IEI at a tertiary-level academic hospital in Malaysia. Review of medical records of all cases of IEI who underwent HSCT between January 1993 and December 2018 at our centre. Diagnoses, complications, HSCT protocols and outcome data were studied. There were 20 patients (19 boys) with a median age at diagnosis of 11 months (range: 2 months to 12 years). Eleven of 19 (58%) had malnutrition at presentation. Donor sources were variable: 13 (65%) matched sibling donor (MSD), 4 (20%) human leukocyte antigen-haploidentical donor (HD) and 3 (15%) matched unrelated donor (MUD). Conditioning regimens were physician-dependent and adapted to each patient's clinical status. Grades III-IV acute graft-versus-host disease occurred in two of three cases who received MUD grafts, 50% in those who received HD, and 8% in the MSD group. Transplant-related mortality at day +100 was 5%. With a median follow-up of 7.5 years, 18 (90%) patients are alive and free of infections. Outcome of HSCT for IEI in our centre is comparable with international reports. HSCT results using HD and MUD grafts are also good despite challenges from acute graft-versus-host disease, providing a feasible alternative for patients without matched donors.

Increased Coffee Intake Reduces Circulating HBV DNA and HBsAg Levels in HBeAg-Negative Infection: A Cohort Study.

Coffee is hepatoprotective and potentially antiviral; however, its anti-hepatitis B virus (anti-HBV) property is not known in humans. This study investigated the influence of coffee drinking behaviour as well as clinical and biochemical profiles of hepatitis B e antigen (HBeAg) negative participants on circulating HBV DNA and hepatitis B surface antigen (HBsAg) levels at a 24-week interval. Exactly 114 chronically HBV-infected adult participants were enrolled from the University of Malaya Medical Centre (UMMC), Malaysia. A significant reduction of HBV DNA level was observed in those drinking three or more cups of coffee per day, with a median reduction of 523 IU/mL (P = 0.003). Reduction of HBsAg level was observed in those drinking two cups per day, with a median reduction of 37 IU/mL (P < 0.001). Multivariate analysis showed that increased coffee intake (P = 0.015) and lower ALT level (P = 0.033) were the significant predictors for a lower HBV DNA level, whereas increased coffee intake (P = 0.002) and having a family history of HBV infection (P = 0.021) were the significant predictors for a lower HBsAg level. These data suggest that drinking three cups or more coffee per day reduces circulating HBV DNA and HBsAg levels.

Validity and reliability of the Neuropsychological Assessment Battery – Screening Module (S-NAB) in a subset of Malaysian population with mild traumatic brain injury (mTBI)

This study assessed the validity (construct validity) and reliability (internal consistency) of the Neuropsychological Assessment Battery Screening Module (S-NAB) in detecting mild cognitive deficit/alteration in multicultural, multilingual, and multiethnic mild traumatic brain injury (mTBI) population of Malaysia. S-NAB and Montreal Cognitive Assessment (MoCA) data from 114 patients with mTBI (93 males; 21 females) aged 18 to 60 years old were obtained at University Malaya Medical Center, Malaysia. The mean age was 28.17 ± 8.57 years and mean education years was 12.40 ± 2.01. Convergent validity was assessed between S-NAB domain scores and MoCA total scores by using Pearson’s correlation and internal consistency was assessed using Cronbach’s alpha. Acceptable internal consistency (α ≥ .70) was found for Attention, Language, and Memory domains but weak internal consistencies (α < .50) were found for Spatial and Executive Function domains. There were positive but weak correlations between S-NAB and MoCA. These findings provide some support for the application of S-NAB in assessing mild cognitive deficits of mTBI population in a Malaysian setting.