Singapore, 15 November 2022 – A multinational research team of clinicians and scientists led by the National Cancer Centre Singapore (NCCS) has trained a genomic model to be able to more precisely determine the prognosis of Natural-killer/T cell lymphoma (NKTCL) patients. These findings, published in the American Journal of Hematology on 16 June 2022, could help steer a more personalised approach for the treatment of NKTCL.
NKTCL is an Asian-prevalent, non-Hodgkin lymphoma that develops outside the lymph nodes, commonly found in the nasal area. Associated with Epstein–Barr virus (EBV), relapse for NKTCL disease is common and survival rates are low, especially in late stage disease. The global 5-year overall survival rate is 70% in patients with early stage disease and less than 50% in patients with late stage disease. Better patient stratification approaches for NKTCL are needed so that treatment strategies can be personalised based on individual risk.
Building a genomic prognostic model
Caption: (Left) A CT scan of a NKTCL patient’s cranium and (Right) their tumour samples amplified under a microscope.
Several prognostic models have been developed to guide disease management for patients with NKTCL using risk adapted approaches. In particular, the Prognostic Index for Natural-Killer cell lymphoma (PINK) incorporates clinical risk factors such as advanced age (>60 years old), disease stage, nodal status, and non-nasal type of disease. While PINK and other prediction models are used to determine NKTCL prognosis, advances in genetic profiling and lower costs of sequencing have led to the discovery of new drivers of disease, including somatic mutations and germline polymorphisms. These findings called for the development of a genomic prognostic model (GPM) to be used alongside more established prediction models.
Answering this call, a research team led by NCCS, in collaboration with Singapore General Hospital (SGH), National University Cancer Institute, Singapore (NCIS) and A*STAR’s Genome Institute of Singapore (GIS) used next-generation sequencing to identify somatic mutations in NKTCL tumours in 260 patients from Singapore, China, Belgium and Taiwan. Using their genomic mutations and survival data, a GPM consisting of the mutational status of 13 prognostic genes was trained to effectively predict for the worst clinical outcomes.
Using the model to understand and treat NKTCL
“The gene set we identified when developing the genomic prognostic model can be built into existing prognostic models or used alongside current prognostic models for NKTCL. This should significantly improve the accuracy of disease prognosis and prediction,” said senior author of the study, Associate Professor Ong Choon Kiat, Principal Investigator of the Lymphoma Genomic Translational Research Laboratory, NCCS.
The survival of early stage NKTCL patients, when treated with a combination of chemotherapy and radiotherapy, is typically good1. However, around 20 to 30% of this group will relapse and have poor outcomes. The 13 prognostic genes discovered in building the GPM can be used for early identification of this group of patients even before they have relapsed, so that targeted and more aggressive therapy can be started.
“In the past, we would not have much recourse for NKTCL patients who relapse. Now that we have a way to identify who is likely to suffer a relapse, we can institute personalised treatment early by trying more aggressive frontline therapies or immunotherapy to improve their survival,” said co-author of the study, Professor Lim Soon Thye, Deputy Group Chief Executive Officer (Research and Education), SingHealth and Deputy Chief Executive Officer (Clinical), NCCS.
In addition to personalising treatment, the GPM also allows clinicians to refer patients who are at greater risk of poor outcomes for clinical trials even if they are in the early stage of disease.
The team now plans to conduct large-scale prospective cohort studies using the GPM, to further confirm its application and usefulness in real-world clinical settings.
This research is supported by the National Research Foundation Singapore under its Open Fund-Large Collaborative Grant (NMRC-OFLCG-18May0028) which is administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), the Tanoto Professorship in Medical Oncology and a number of other funding sources.
1Kwong, Y. L., Kim, S. J., Tse, E., Oh, S. Y., Kwak, J. Y., Eom, H. S., Do, Y. R., Mun, Y. C., Lee, S. R., Shin, H. J., Suh, C., Chuang, S. S., Lee, Y. S., Lim, S. T., Izutsu, K., Suzuki, R., Relander, T., d’Amore, F., Schmitz, N., … Kim, W. S. (2018). Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma. Annals of Oncology, 29(1), 256–263. https://doi.org/10.1093/annonc/mdx684
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The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. NCCS attends to the majority of cancer cases in Singapore’s public healthcare sector. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve the vision of being a global leading cancer centre, NCCS offers world class care and shares its depth of experience and expertise by training local and overseas medical professionals.
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