METHODS: The performance of a custom, in-house designed 22-gene NGS panel was technically validated using reference standards across two independent replicate runs. The panel was subsequently used to screen a total of 10 clinical MPN samples (ET n = 3, PV n = 3, PMF n = 4). The resulting NGS data was then analysed via a bioinformatics pipeline.
RESULTS: The custom NGS panel had a detection limit of 1% variant allele frequency (VAF). A total of 20 unique variants with VAFs above 5% (4 of which were putatively novel variants with potential biological significance) and one pathogenic variant with a VAF of between 1 and 5% were identified across all of the clinical MPN samples. All single nucleotide variants with VAFs ≥ 15% were confirmed via Sanger sequencing.
CONCLUSIONS: The high fidelity of the NGS analysis and the identification of known and novel variants in this study cohort support its potential clinical utility in the management of MPNs. However, further optimisation is needed to avoid false negatives in regions with low sequencing coverage, especially for the detection of driver mutations in MPL.
METHODS: Through the Association of Southeast Asian Nations Costs in Oncology study, 1490 newly diagnosed cancer patients were followed-up in Malaysia for 1 year. Health-related quality of life was assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EuroQol-5 (EQ-5D) dimension questionnaires at baseline, 3 and 12 months. Psychological distress was assessed by using Hospital Anxiety and Depression Scale. Data were modeled by using general linear and logistic regressions analyses.
RESULTS: One year after diagnosis, the mean EORTC QLQ-C30 Global Health score of the cancer survivors remained low at 53.0 over 100 (SD 21.4). Fifty-four percent of survivors reported at least moderate levels of anxiety, while 27% had at least moderate levels of depression. Late stage at diagnosis was the strongest predictor of low HRQoL. Increasing age, being married, high-income status, hospital type, presence of comorbidities, and chemotherapy administration were also associated with worse HRQoL. The significant predictors of psychological distress were cancer stage and hospital type.
CONCLUSION: Cancer survivors in this middle-income setting have persistently impaired HRQoL and high levels of psychological distress. Development of a holistic cancer survivorship program addressing wider aspects of well-being is urgently needed in our settings.
METHODS: Through the Association of Southeast Asian Nations Costs in Oncology study, 1,294 newly diagnosed patients with cancer (Ministry of Health [MOH] hospitals [n = 577], a public university hospital [n = 642], private hospitals [n = 75]) were observed in Malaysia. Cost diaries and questionnaires were used to measure incidence of financial toxicity, encompassing financial catastrophe (FC; out-of-pocket costs ≥ 30% of annual household income), medical impoverishment (decrease in household income from above the national poverty line to below that line after subtraction of cancer-related costs), and economic hardship (inability to make necessary household payments). Predictors of financial toxicity were determined using multivariable analyses.
RESULTS: One fifth of patients had private health insurance. Incidence of FC at 1 year was 51% (MOH hospitals, 33%; public university hospital, 65%; private hospitals, 72%). Thirty-three percent of households were impoverished at 1 year. Economic hardship was reported by 47% of families. Risk of FC attributed to conventional medical care alone was 18% (MOH hospitals, 5%; public university hospital, 24%; private hospitals, 67%). Inclusion of expenditures on nonmedical goods and services inflated the risk of financial toxicity in public hospitals. Low-income status, type of hospital, and lack of health insurance were strong predictors of FC.
CONCLUSION: Patients with cancer may not be fully protected against financial hardships, even in settings with universal health coverage. Nonmedical costs also contribute as important drivers of financial toxicity in these settings.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
Materials and methods: This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia.
Results: A total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p