Precision Radiotherapeutics and Oncology Programme

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The focus of our laboratories, which is led by two clinician-scientists, centres on three main domains in two dominant cancers in Singapore—nasopharynx (NPC) and prostate cancer (3rd most common. These domains are: 

1. To design and conduct novel phase II and III clinical trials in NPC and prostate cancers; 
2. To leverage on contemporary molecular genomics and sequencing techniques to derive novel biomarkers of tumour aggression and radio-resistance; 
3. To explore “Big Data” science to develop risk stratification models for precision medicine strategies.

Our research activities are largely funded by several national-level, institutional, and philanthropy grants (NMRC OF-LCG, NMRC CTG-IIT, NMRC OF-IRG, NMRC CSA, Kua Hong Pak Head and Neck Cancer Research Programme). Of note, we currently co-lead the Singapore NPC Large Collaborative Grant (Tier 1 funding:10M SGD), where our group leads a platform trial – RIBBON: tReatment Individualisation By eBv stratificatiON in Locally Advanced nasopharyngeal carcinoma: A multi-arm platform study – for locoregionally advanced NPC and recurrent-metastatic NPC (NCT05517135, clinicaltrials.gov).  

Amongst our key discoveries in the different topics, our group has;

1. For NPC and PCa, built a cancer-specific tissue and data repository since 2017, comprising >1,000 patients per cancer, with matched clinical and genomics data, along with longitudinal outcomes; 
2. Constructed several publicly available online tools, including a novel clinicomolecular risk grouping of localised NPC patients for individualised treatment strategies (Chen FP, et al. Therapeutic Advances in Medical Oncology, 2021); a risk prediction model for individualised selection of patients with locoregional recurrent NPC to re-irradiation (PRANCIS: Prediction of RAdioresistant Nasopharyngeal CarcInoma Survival; www.PRANCIS.Medlever.com; Li YQ et al. Journal of Clinical Oncology, 2018); we had also developed a novel phenotypic classification of patients with locoregionally-advanced NPC based on real-time tracking of treatment response with plasma cell-free EBV DNA (Lv JW et al., Nature Communications, 2019); 
3. Completed several phase 2 and 3 clinical trials in advanced NPC that led to shifts in standards of care; among the pivotal trials were a) demonstrating the survival advantage with the use of induction chemotherapy in stage 3-4 NPC (Zhang Y et al., New England Journal of Medicine, 2019) and b) demonstrating the survival advantage with local radiotherapy in metastatic NPC patients (You R et al., JAMA Oncology, 2020); 
4. Participated in multi-national consortium-based projects such as the Head and Neck Cancer Radiogenomics Consortium and published on 2 pieces of work that identified a number of low penetrant gene loci that could predict the risk of acute toxicities following head and neck radiotherapy (Naderi et al., Radiotherapy and Oncology, 2022; Schack et al., British Journal of Cancer, 2022). We are now also part of a larger meta-analysis that is currently ongoing.

Selected publications:

1. Zhang Y, Chen L, Hu GQ … Chua ML, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. New England Journal of Medicine. 2019 Sep 19;381(12):1124-35. JIF: 176.079 
2. You R, Liu YP, Huang PY … Chua ML, et al. Efficacy and safety of locoregional radiotherapy with chemotherapy vs chemotherapy alone in de novo metastatic nasopharyngeal carcinoma: a multicenter phase 3 randomized clinical trial. JAMA oncology. 2020 Sep 1;6(9):1345-52. JIF: 33.006 
3. Miao J, Wang L, Tan SH … Chua ML, et al. Adjuvant capecitabine following concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a randomized clinical trial. JAMA oncology. 2022 Dec 1;8(12):1776-85. JIF: 33.006 
4. Chua ML, Wee JT, Hui EP. Chan AT. Nasopharyngeal carcinoma. The Lancet. 2016;387:1012-24. JIF: 202.731 
5. Chua ML, Lee VH, Lee AW. Hyperfractionation for reirradiation of recurrent nasopharyngeal carcinoma. The Lancet. 2023 Mar 18;401(10380):878-9. JIF: 202.731 
6. Yip PL, Lee AW, Chua ML. Adjuvant chemotherapy in nasopharyngeal carcinoma. The Lancet Oncology. 2023 Jun 2. JIF: 54.433 
7. Chen YP, Ismaila N, Chua ML, Colevas AD, Haddad R, Huang SH, Wee JT, Whitley AC, Yi JL, Yom SS, Chan AT. Chemotherapy in combination with radiotherapy for definitive-intent treatment of stage II-IVA nasopharyngeal carcinoma: CSCO and ASCO guideline. Journal of Clinical Oncology. 2021 Mar 1;39(7):840-59. JIF: 50.739 
8. Lv J, Chen Y, Zhou G … Chua ML, et al. Liquid biopsy tracking during sequential chemo-radiotherapy identifies distinct prognostic phenotypes in nasopharyngeal carcinoma. Nature communications. 2019 Sep 2;10(1):3941. JIF: 17.694 
9. Fraser M, Sabelnykova VY, Yamaguchi TN … Chua ML, et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature. 2017 Jan 19;541(7637):359-64. JIF: 69.504 
   
10. Espiritu SM, Liu LY, Rubanova Y … Chua ML, et al. The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell. 2018 May 3;173(4):1003-13. JIF: 66.85